Journal of Macromolecular Science, Part B

Physics

ISSN: (Print) (Online) Journal homepage: www.tandfonline.com/journals/lmsb20

Nano-Bio Interfaces: Pioneering Targeted

Approaches for Disease Treatment and Prevention

Dilpreet Singh

To cite this article: Dilpreet Singh (28 Aug 2024): Nano-Bio Interfaces: Pioneering Targeted
Approaches for Disease Treatment and Prevention, Journal of Macromolecular Science, Part B,
DOI: 10.1080/00222348.2024.2395693

To link to this article: https://doi.org/10.1080/00222348.2024.2395693

Published online: 28 Aug 2024.

Submit your article to this journal

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=lmsb20
JOURNAL OF MACROMOLECULAR SCIENCE, PART B
https://doi.org/10.1080/00222348.2024.2395693

Nano-Bio Interfaces: Pioneering Targeted Approaches for

Disease Treatment and Prevention
Dilpreet Singha,b
a
University Institute of Pharma Sciences, Chandigarh University, Mohali, India; bUniversity Centre for
Research and Development, Chandigarh University, Mohali, India

ABSTRACT ARTICLE HISTORY

Nanotechnology has emerged as a pivotal force in biomedical Received 2 August 2024
research, offering groundbreaking solutions for disease treatment Accepted 19 August 2024
and prevention through the integration of nanoscience with biology.
KEYWORDS
This review explores the multifaceted applications of nano-bio inter­
Nano-bio interfaces;
faces in revolutionizing therapeutic interventions and public health nanotechnology; disease
strategies. At the forefront of innovation, nanomaterial-based drug therapy; disease prevention;
delivery systems demonstrate unparalleled precision and efficacy in drug delivery systems;
targeted drug delivery, minimizing systemic toxicity and maximizing precision medicine;
therapeutic outcomes. Furthermore, the development of multifunc­ personalized healthcare;
tional nanoparticles capable of simultaneous drug delivery and diag­ vaccine development;
nostic imaging enables real-time monitoring of treatment responses, immunotherapy; targeted
heralding a new era of personalized medicine. Nano-bio interfaces drug delivery; diagnostics;
also play a crucial role in advancing vaccine development and immu­ antimicrobial nanomaterials;
infection control;
notherapies, with nanoparticle-based vaccine platforms offering multidisciplinary collabor­
enhanced antigen delivery and immune stimulation for robust and ation; biomedical research;
durable immune responses against infectious diseases and cancer. In public health
the realm of disease prevention, antimicrobial nanomaterials provide
effective strategies for infection control, while nanovaccines and
prophylactic drug delivery systems offer tailored solutions for miti­
gating the spread of infectious agents. Through a comprehensive
exploration of these pioneering approaches, this review, we believe,
highlights the transformative potential of nano-bio interfaces in
reshaping the landscape of disease treatment and prevention.

1. Introduction
Nanotechnology has ushered in a new era in biomedical science, revolutionizing the
landscape of disease treatment and prevention. By seamlessly integrating the principles
of nanoscience with biology, nano-bio interfaces have emerged as powerful tools with
the potential to address some of the most pressing challenges in healthcare [1].1 This
review article aims to provide a comprehensive overview of the pioneering approaches
facilitated by nano-bio interfaces in the realms of disease treatment and prevention. The
convergence of nanotechnology and biology has paved the way for innovative strategies
that leverage the unique properties of nanomaterials to overcome traditional limitations
in therapeutic interventions [2]. One of the most transformative applications lies in

CONTACT Dilpreet Singh [email protected] Department of Pharmaceutics, University Institute of

Pharmaceutical Sciences, Chandigarh University, Mohali, India
� 2024 Taylor & Francis Group, LLC
2 D. SINGH

drug delivery systems, where nanocarriers such as liposomes, polymeric nanoparticles

and dendrimers offer targeted and controlled release of therapeutic agents, minimizing
off-target effects and improving their efficacy [2,3]. Additionally, the development of
multifunctional nanoparticles capable of simultaneous drug delivery and diagnostic
imaging has opened new avenues for personalized medicine and precision therapeu­
tics [3].
Beyond drug delivery, nano-bio interfaces have also revolutionized approaches to dis­
ease diagnosis and imaging. Nanoparticles engineered for specific targeting and imaging
modalities, such as quantum dots and iron oxide nanoparticles, enable early detection
of diseases and precise visualization of pathological processes at the molecular level [4].
This integration of diagnostics with therapeutic interventions not only enhances treat­
ment efficacy but also facilitates real-time monitoring of treatment responses, enabling
timely adjustments for optimized outcomes [5]. Moreover, nano-bio interfaces hold
immense promise for the development of next-generation vaccines and immunothera­
pies. Nanoparticle-based vaccine platforms offer enhanced antigen delivery, immune
stimulation and stability, leading to potent and durable immune responses against infec­
tious diseases, cancer and autoimmune disorders. Furthermore, the advent of immuno­
modulatory nanoparticles capable of reprogramming immune cell functions opens new
avenues for combating immunosuppressive microenvironments in cancer and chronic
infections. In the realm of disease prevention, nano-bio interfaces offer novel
approaches to infection control and prophylactic interventions [6]. Antimicrobial nano­
materials, including silver nanoparticles and nanostructured surfaces, exhibit potent
activity against a broad spectrum of pathogens, thereby reducing the risk of healthcare-
associated infections and community outbreaks [7].
Additionally, the development of nanovaccines and prophylactic drug delivery sys­
tems provides targeted and sustained protection against infectious agents, bolstering
public health efforts to mitigate the spread of infectious diseases [8]. Overall, the inter­
disciplinary nature of nano-bio interfaces underscores their transformative potential in
reshaping the landscape of disease treatment and prevention. By elucidating the mecha­
nisms and applications of nanotechnology in biomedical research, this review aims to
highlight the pivotal role of nano-bio interfaces in driving innovation and advancing
healthcare solutions for the benefit of society.

1.1. Theoretical foundations of nano-bio interfaces

The theoretical foundations of nano-bio interfaces form the cornerstone of integrating
nanotechnology with biological systems, offering unparalleled opportunities in medical
science [9]. These basic foundations between nanotechnology and biointerfaces provide
new concepts and applications in the pharmaceutical field which are depicted are
Table 1. The provided information helps in selecting multifunctional nanomaterials and
their biophysical properties and provides new approaches for targeted delivery in the
body to combat diseases. Nanoparticles, owing to their size, exhibit quantum effects and
a high surface area to volume ratio, which can be exploited to interact with biological
molecules in ways that were previously unattainable [10,11]. These interactions at the
nano-bio interface, whether through physical adsorption, chemical bonding or biological
 JOURNAL OF MACROMOLECULAR SCIENCE, PART B 3

Table 1. Depiction of theoretical foundations of nano-biointerfaces and their applications in generat­

ing nano-drug delivery systems.
Application in Nano-bio
Theoretical Foundation Description Key Concepts/Theories Interfaces
Quantum Mechanics Describes the behavior of Wave-particle duality, Understanding electronic
particles at the quantum states, properties of
nanoscale, where probability distributions nanomaterials, quantum
classical mechanics is confinement effects
inadequate.
Molecular Biology Studies biological processes DNA replication, protein Designing nanoparticles for
at the molecular level, synthesis, gene targeted drug delivery,
providing insights into expression, cell signaling gene therapy
cellular structure and pathways
function.
Materials Science Investigates the structure, Crystal structure, defects, Engineering nanomaterials
properties, and phase transitions, with desired properties
processing of materials, mechanical properties for biomedical
including nanomaterials. applications
Surface Chemistry Focuses on interactions Adsorption, surface energy, Modifying nanoparticle
that occur at interfaces, surface functionalization, surfaces for enhanced
crucial for self-assembly biocompatibility and
understanding targeting
nanomaterial behavior.
Biophysics Applies physical principles Protein folding, membrane Understanding interactions
to biological systems, biophysics, ion channels, between nanoparticles
studying phenomena molecular motors and biological molecules
such as molecular
dynamics.
Pharmacokinetics Examines the absorption, ADME parameters, drug Predicting and optimizing
distribution, metabolism, bioavailability, clearance drug delivery kinetics
and excretion of drugs mechanisms, drug-drug and efficacy
in the body. interactions
Immunology Studies the immune Antigen recognition, Designing nanoparticles to
system and its response immune cell activation, enhance vaccine efficacy
to foreign substances, antibody production, and immunotherapeutic
crucial for vaccine immune memory responses
development.
Nanotoxicology Investigates the potential Cellular uptake Assessing the safety and
adverse effects of mechanisms, cytotoxicity biocompatibility of
nanomaterials on pathways, long-term nanoparticles for
biological systems and biodistribution, biomedical applications
the environment. environmental impact
Bioinformatics Integrates biological data Sequence analysis, Designing nanoparticles for
with computational structural prediction, targeted drug delivery
tools to analyze and systems biology based on molecular
interpret complex modeling, drug design interactions
biological systems.

recognition, are critical in dictating the functionality of nanomaterials in diagnostics,

drug delivery and therapy [2]. Understanding these mechanisms—how nanoparticles
can be designed to navigate through biological fluids, target specific cells or tissues,
evade the immune system and deliver therapeutic agents directly to the site of disease—
is fundamental to advancing the field of nanomedicine [12].
The provided table (Table 1) also covers the selection and design criteria of materials
for nano-bio applications, emphasizing the importance of biocompatibility, targeting
efficiency, and controlled release capabilities. Material science plays a pivotal role in the
development of nano-bio interfaces, with a variety of organic, inorganic, and hybrid
materials being engineered to achieve optimal interactions with biological systems
[13,14]. These materials are tailored for specific applications, ranging from metallic
4 D. SINGH

nanoparticles for imaging and therapy to polymeric nanocarriers for drug delivery, each
chosen based on their unique properties, such as magnetic responsiveness, optical char­
acteristics and biodegradability [15]. The exploration of theoretical foundations not only
underscores the complexity and potential of nano-bio interfaces but also sets the stage
for their practical applications in disease diagnosis, treatment, and prevention, charting
the path for future innovations in nanomedicine.
Figure 1 depicts a generalized pictorial depiction of nano-biointerface systems. The
image represents a conceptual illustration of nano-biointerface technology, depicting the
interaction between nanomaterials and biological entities at the nanoscale. The purple
area with a hexagonal pattern likely represents a cell membrane, the boundary of a bio­
logical cell. The hexagonal structures symbolizes the lipid bilayer, which is a crucial
component of cell membranes. The cylindrical chain-like structure (Center) connecting
the nanoparticle cluster to another component on the right may represent nanocarriers.
These molecules could be designed to attach to specific receptors on the cell membrane.
The green structures connected (center part) to the nanocarriers could represent
ligands, which are molecules that can bind to specific receptors on the cell membrane.

Figure 1. Visual representation of nano-biointerface technology, where a multicolored nanoparticle

cluster on the left, comprising various functional molecules like therapeutic agents and targeting
ligands, interacts with a cell membrane depicted in purple with a hexagonal lipid bilayer structure.
The interaction is facilitated by green and blue chain-like nanocarriers, connected by orange joints
(orange circular structure), which bridge the nanoparticle to the cell membrane. The green structures
highlight ligands that bind to specific receptors on the cell, leading to targeted delivery into the blue
cellular interior on the right.
 JOURNAL OF MACROMOLECULAR SCIENCE, PART B 5

This interaction is crucial for targeted delivery, where the nanoparticles are directed
specifically to certain cells. The blue circular structure on the far right might represent
the cell’s interior or a specific organelle within the cell where nanocluster produces tar­
get selectivity. The interaction depicted here suggests that the nanoparticles have suc­
cessfully targeted the cell. The area where the nanocarrier meets the cell membrane
shows a detailed interaction interface (upper right sharp blue colored thin layer).

1.2. Nanotechnology in disease diagnosis

Nanotechnology in disease diagnosis represents a transformative shift toward more
precise, sensitive, and earlier detection of diseases [16]. Utilizing nanosensors, the cut­
ting-edge developments in biomarker detection and disease diagnostics provide recent
developments and tailored enhanced sensitivity and detectability [17]. Nanosensors,
with their high surface area and enhanced reactivity, offer unparalleled sensitivity in
identifying biomolecules at extremely low concentrations, enabling the detection of dis­
eases at their nascent stages [18,19]. This capability is pivotal for conditions like cancer
and neurodegenerative diseases, where early detection can significantly improve progno­
sis and treatment outcomes [20]. Techniques such as quantum dots and magnetic nano­
particles enhance contrast and provide detailed images of biological structures,
facilitating the identification of pathological changes well before they manifest into clin­
ical symptoms [21,22]. Quantum dots are semiconductor nanocrystals that have unique
optical properties, including size-tunable fluorescence emission. When excited by a light
source, quantum dots emit light at specific wavelengths that depend on their size [22].
Magnetic nanoparticles can act as contrast agents in Magnetic Resonance Imaging
(MRI). When magnetic nanoparticles accumulate in a specific area of the body (such as
a tumor), they alter the local magnetic field, enhancing the contrast in MRI images and
allowing for better visualization of the target tissue [23].
Various case studies on the early detection of cancer and the monitoring of neurode­
generative diseases have also been provided [24–26]. The first case study was done by
the researchers for the quantum dots which exhibited strong fluorescence signals upon
binding to HER2-positive cells, allowing for clear differentiation between cancerous and
non-cancerous cells [24,25]. For magnetic nanoparticles, the nanodiagnostics technique
provided significant contrast enhancement in MRI images, allowing for clear visualiza­
tion of amyloid-beta plaques. Plaques were detected at an early stage of disease progres­
sion, before the onset of significant cognitive impairment [26].

1.3. Nano-biointerface derived nanomaterials for drug delivery

Nanobiointerfaces constitute the complex interactions between nanomaterials and bio­
logical entities, which are central to the engineering and efficacy of advanced drug deliv­
ery systems [27,28]. These interfaces enable critical interactions with various biological
components such as cells, tissues, proteins, and nucleic acids. Such interactions signifi­
cantly influence the effectiveness, biocompatibility, and targeting precision of nanoscale
drug carriers [29]. To enhance these capabilities, various nanomaterials are subjected to
surface functionalization, a process in which materials are coated with biomolecules,
6 D. SINGH

Table 2. Different types of nanomaterials investigated for targeted applications using nano-biointer­
face technology.
Nanomaterial Composition Size Range Surface Functionalization Loading Capacity Ref
Liposomes Phospholipid bilayers 50 - 200 nm PEGylation, ligands High [38]
Polymeric Synthetic polymers 10 - 200 nm Surface modification, ligands Moderate to high [39]
Nanoparticles
Dendrimers Branching macromolecules 1 - 10 nm Surface functionalization High [40]
Micelles Amphiphilic molecules 10 - 100 nm PEGylation, ligands Moderate [41]
Nanoparticles Inorganic materials 1 - 100 nm Surface modification, ligands High [42]
Carbon Nanotubes Cylindrical carbon structures 1 - 100 nm Functional groups, biomolecules High [43]
Mesoporous Silica Porous silica structure 50 - 200 nm Surface modification High [44]
Gold Nanoparticles Gold atoms 1 - 100 nm Thiolation, biomolecules Low to moderate [45]
Quantum Dots Semiconductor nanocrystals 2 - 10 nm Surface modification, ligands High [46]
Iron Oxide Iron oxide core 5 - 100 nm Surface coating, ligands Moderate [47]
Nanoparticles

like peptides, antibodies, or Aptamers [30,31]. This modification not only improves tar­
geting accuracy but also increases the biocompatibility of the nanocarriers. Moreover,
the physicochemical attributes of these nanomaterials—such as size, shape, surface
charge, and hydrophobicity—play vital roles in determining their biological interactions
[32,33]. By fine-tuning these properties, researchers can optimize drug delivery kinetics,
cellular uptake, and therapeutic outcomes, thereby advancing the development of more
efficient drug delivery mechanisms [34].
Furthermore, nanobiointerfaces play a crucial role in mediating cellular signaling
pathways, immune responses, and biodegradation processes, thereby influencing the
overall safety and efficacy of drug delivery systems [35,36]. By harnessing the principles
of nanobiointerfaces, researchers can develop next-generation drug delivery platforms
capable of precise targeting, controlled release, and enhanced therapeutic outcomes
while minimizing off-target effects and systemic toxicity [37]. The different types of
nanobiointerfaces derived drug delivery systems and their pharmaceutical depiction are
depicted in Table 2. The myriad of nanocarriers were designed for the precise delivery
of drugs to targeted sites within the body [48–50]. The structural depiction of the differ­
ent types of carriers is depicted in Figure 2. The image showcases various nanocarriers
used in nanobiointerface-derived drug delivery systems. It includes lipid-based nanopar­
ticles like liposomes and hydrogel nanoparticle (A-B) for enhancing solubility and bio­
availability, and polymeric nanoparticle, dendrimers and fullerene (C-E) which offer a
high surface area for drug loading and for controlled drug release. The figure also pro­
vides the critical structures of Polymeric Micelles (F) Virus-Like Particles (VLP) (G)
and Nanoparticle-Based Adjuvants (H), all of which are used to solubilize hydrophobic
drug and are used in vaccine delivery and gene therapy [51]. Some advanced modofica­
tions in structural characteristics in nanobiointerfaces technology led to development of
Star Polymer (I), PEGylated Nanoparticle (J) and Metal Oxide Nanoparticle (K) associ­
ated with high targeting capacity [52]. Mesoporous silica nanoparticle (L) and Polymer
Drug Conjugates (M) are used in imaging, drug delivery, and as contrast agents due to
their unique optical and magnetic properties. Nanoporous particles (N) and Metallic
nanoparticles (O) used as a carrier for drugs, genes, or imaging agents due to its high
surface area and functionalization possibilities [53,54].
 JOURNAL OF MACROMOLECULAR SCIENCE, PART B 7

Figure 2. Various structural depiction of nanomaterials and nanocarriers (labeled as A-O) utilized
through nano-biointerfaces for different drug delivery applications.

The mechanisms behind targeted drug delivery by using these carriers have multiple
strategies which have been employed to achieve site-specific actions. This includes the
use of ligands on nanoparticle surfaces that bind to specific receptors on target cells,
enabling the direct delivery of drugs to diseased cells while sparing healthy ones [55,56].
Such targeted approaches are particularly crucial in the treatment of cancer, where min­
imizing damage to healthy tissues is of paramount importance [57,58]. The blood-brain
barrier, for example, has been a formidable obstacle in treating neurological disorders.
Nanoparticles are being developed to navigate this barrier, delivering therapeutic agents
directly to the brain and opening new frontiers in the treatment of Alzheimer’s,
Parkinson’s, and other neurodegenerative diseases [59]. Further approaches includes
generation of key targeted platforms, like stimuli-responsive systems, which release their
payload in response to specific physiological triggers, such as pH changes, temperature
fluctuations or enzymatic activity, offering controlled and sustained release of drugs
[60]. The enzymatic activity can serve as a trigger in enzyme-sensitive systems, where
the presence of certain enzymes, often overexpressed in disease states, leads to the
breakdown of the carrier and subsequent release of the drug.

1.4. Pharmaceutical applications of nano-biointerfaces in various fields

1.4.1. Nano-Bio interfaces in targeted therapies
Nano-bio interfaces in therapy represent a paradigm shift in the approach to treating
diseases, offering innovative strategies that leverage the unique properties of nanomate­
rials to enhance therapeutic outcomes [61]. The multifaceted applications of
8 D. SINGH

nanotechnology in therapy, spanning from gene therapy to photothermal and photo­

dynamic therapy, are illustrated in Table 3. Gene therapy, enabled by nanotechnology,
holds immense promise for treating genetic disorders, cancer, and infectious diseases
[62]. Nanoparticles serve as vectors for delivering therapeutic genes to target cells, over­
coming challenges such as immune rejection and off-target effects [63,64]. Viral vectors,
such as adenoviruses, lentiviruses, and adeno-associated viruses (AAV), are highly effi­
cient in transducing cells due to their evolved mechanisms for entering host cells and
integrating genetic material [65]. Adenoviruses are known for their high transduction
efficiency and capacity for large genetic payloads, though they can provoke strong
immune responses. Lentiviruses integrate into the host genome, enabling long-term
expression of the therapeutic gene but posing a risk of insertional mutagenesis [66,67].
AAV vectors are favored for their low immunogenicity and ability to transduce both
dividing and non-dividing cells, though they have limited cargo capacity [68]. Non-viral
vectors, including plasmid DNA, liposomes, and polymer-based systems, offer safer
alternatives with reduced immunogenicity and lower risk of insertional mutagen­
esis [69].
Photothermal and photodynamic therapies harness the optical properties of nanopar­
ticles to selectively destroy diseased cells while sparing healthy tissue. Photothermal
therapy utilizes nanoparticles that absorb light and convert it into heat, leading to local­
ized hyperthermia and cell death [70]. Photodynamic therapy, on the other hand,
involves the activation of photosensitive agents by light, generating reactive oxygen spe­
cies that induce cell death [71,72]. Both approaches offer precise and minimally invasive
alternatives to traditional cancer treatments, with the potential for synergistic effects
when combined with other therapies [73]. Organic nanoparticles and nanocrystals can
be designed to enhance immune activation against tumors or to suppress immune reac­
tions in autoimmune diseases, offering tailored approaches to immuno-oncology and
autoimmune disorders [74].

1.4.2. Nano-Bio strategies for disease prevention

Nano-biointerfaces have emerged as a promising tool in disease prevention, offering
innovative strategies for vaccine development, infection control and prophylactic inter­
ventions. Table 4 compiles the different pharmaceutical aspects of various nano-biointe­
face derived strategies and their applications in disease prevention [74, 79]. Vaccine
development stands at the forefront of disease prevention and nanotechnology has
opened new avenues for enhancing vaccine efficacy and delivery [79]. Nanoparticle-
based vaccine platforms enable targeted antigen delivery, controlled release and potent
immune stimulation, leading to improved vaccine responses and broader protection
against infectious diseases [80,81]. The design principles and applications of nanopar­
ticle vaccines have shown effectiveness in-vivo in combating viral, bacterial and parasitic
pathogens. In addition to vaccine development, nanotechnology offers novel approaches
to infection control and prevention [82,83]. Nanoparticles encapsulate antigens and are
often coated with adjuvants to enhance immunogenicity. These nanoparticles are taken
up by antigen-presenting cells (APCs) such as dendritic cells, which process and present
the antigens to T-cells, thereby stimulating a robust and long-lasting immune
response [84].
Table 3. Nano-biointerface derived applications in different targeted therapies.
Therapy Type Application Nanomaterial Targeted Diseases Mechanism of Action Current Clinical Stage
Gene Therapy Cancer treatment Lipid nanoparticles Various cancers Modify gene expression in cancerous Phase II
cells
Genetic disorders treatment Polymeric nanoparticles Cystic fibrosis, Duchenne Cellular uptake via receptor-mediated Phase I
muscular dystrophy endocytosis
Infectious diseases treatment Viral vectors [(adenoviruses, HIV, Hepatitis B, Malaria Enhance immune response or correct Phase I
lentiviruses, and viral-induced genetic alterations
adeno-associated viruses
(AAV)]
Photothermal Therapy Cancer treatment Gold nanoparticles Solid tumors Destroying cancer cells through Phase III
localized hyperthermia
Rheumatoid arthritis treatment Carbon nanotubes Inflamed joints Reduce inflammation and pain Preclinical studies
Antibiotic-resistant infections Graphene oxide nanoparticles Bacterial infections Disrupting bacterial cell walls Preclinical studies
Photodynamic Therapy Skin cancer treatment Quantum dots Melanoma, Basal cell Apoptosis in cancerous cells Phase II
carcinoma
Age-related macular degeneration Nanocrystals Macular degeneration Generate Phase I
treatment Reactive Oxygen Species (ROS)
that prevent abnormal blood
vessel growth
Oral cancer treatment Organic nanoparticles Oral squamous cell ROS that selectively kill cancer cells Preclinical studies
carcinoma in the oral cavity.
JOURNAL OF MACROMOLECULAR SCIENCE, PART B
9
 10
D. SINGH

Table 4. Nano-bio strategies for disease prevention.

Application Nano-Bio Strategy Nanomaterials Targeted Pathogens Key Features REF
Vaccine Development Nanoparticle-based vaccine Lipid nanoparticles, Polymeric Viral, Bacterial, Parasitic Targeted antigen delivery, [75]
platforms nanoparticles, Virus-like pathogens controlled release, potent
particles immune stimulation
Infection Control Antimicrobial nanomaterials Silver nanoparticles, Copper Broad spectrum of pathogens Potent antimicrobial activity, [76]
nanoparticles, prevention of microbial
Nanostructured surfaces colonization and
transmission
Prophylactic Interventions Nanoparticle-based drug Liposomes, Dendrimers, Various infectious agents Targeted delivery of [77]
delivery systems Polymer nanoparticles antimicrobial agents,
reduced systemic toxicity
Gene Editing & Gene Silencing Delivery of Gene-Editing Tools Lipid Nanoparticles, Gold Disease-Causing Genes, Cancer Enables precise DNA cuts for [78]
(CRISPR-Cas9) and RNA Nanoparticles, Polymeric Cells gene correction or knockout
Molecules (siRNA) Nanoparticles with CRISPR-Cas9, siRNA
binds to mRNA to prevent
expression of disease-
related genes
 JOURNAL OF MACROMOLECULAR SCIENCE, PART B 11

Antimicrobial nanomaterials, including nanoparticles, nanocomposites and nanostruc­

tured surfaces, exhibit potent antimicrobial activity against a broad spectrum of patho­
gens [85,86]. These materials can be incorporated into medical devices, textiles and
environmental coatings to prevent microbial colonization and transmission, reducing
the risk of healthcare-associated infections and community outbreaks [85,86].
Nanomaterials, like silver, gold, and copper nanoparticles, release metal ions that disrupt
microbial cell membranes, generate reactive oxygen species (ROS) that damage cellular
components, and interfere with microbial DNA replication [87]. Furthermore, nanopar­
ticles serve as versatile platforms for the delivery of prophylactic agents, including anti­
microbial peptides, small molecule inhibitors and immunomodulators. By encapsulating
and targeting these agents to sites of infection or colonization, nanoparticles enhance
their efficacy while minimizing systemic toxicity, offering tailored solutions for prevent­
ing infectious diseases [88,89]. Nanoparticles deliver gene-editing tools (e.g.; CRISPR-
Cas9) or RNA molecules (e.g.; siRNA) into target cells. CRISPR-Cas9 induces precise
cuts in the DNA at specific locations, enabling gene correction or knockout. siRNA
binds to complementary mRNA sequences, leading to their degradation and preventing
the expression of disease-related genes [90].

1.5. Safety, ethics, and Regulatory aspects

Nanobiointerface-derived drug delivery systems hold immense promise for revolutioniz­
ing therapeutic interventions, yet they raise critical concerns regarding safety, ethics,
and regulatory aspects [91,92]. The biocompatibility, biodistribution and long-term fate
of the nanomaterials need to be evaluated in terms of their safety aspects, ensuring they
do not elicit adverse immune responses or accumulate in organs causing toxicity [93].
Safety considerations are paramount, as these nanocarriers interact intricately with bio­
logical systems, potentially leading to unintended toxicological effects [93,94]. The
nano-bio interface’s complexity necessitates rigorous preclinical testing, including in-
vitro and in-vivo models, to understand these interactions comprehensively. Ethically,
the development and deployment of nanobiointerface systems must adhere to principles
of patient safety and informed consent, especially given the novel nature of these tech­
nologies [95]. Researchers and clinicians around the world bear the responsibility of
transparently communicating both the potential risks and benefits of nanobiointerface-
derived therapies to patients, ensuring that individuals are fully informed before con­
senting to treatment. This communication must be clear and thorough, covering not
only the therapeutic advantages but also the possible adverse effects, uncertainties, and
long-term implications of these novel technologies [96]. Furthermore, it is crucial to
address issues of equitable access to these advanced therapies, ensuring that they are
available to all patients, regardless of socioeconomic status, geographical location, or
other factors [97].
Regulatory frameworks play a crucial role in overseeing the safe integration of nano­
biointerfaces into clinical practice [98]. Current guidelines, primarily designed for con­
ventional pharmaceuticals, may not fully address the unique challenges posed by
nanomaterials. Regulatory bodies, like the Food and Drug Administration (FDA) and
the European Medicine Agency (EMA), are working toward updating guidelines to
12 D. SINGH

encompass nanotechnology-specific parameters, including characterization, quality con­

trol and standardization of manufacturing processes [99,100]. These frameworks must
balance innovation with stringent safety assessments to prevent premature or inappro­
priate clinical applications [101]. Collaborative efforts between scientists, ethicists, and
regulators are essential to establish robust safety protocols, ethical guidelines, and regu­
latory standards that keep pace with the rapid advancements in nano-biointerface tech­
nologies [101]. These multidisciplinary collaborations will ensure that the therapeutic
potential of nanobiointerface-derived drug delivery systems is realized in a manner that
prioritizes patient safety, ethical integrity, and public trust [102,103].

2. Conclusions
In conclusion, nano-bio interfaces represent a paradigm shift in disease treatment and
prevention, offering innovative solutions that capitalize on the unique properties of
nanomaterials to address complex biomedical challenges. The diverse applications of
nanotechnology in drug delivery, diagnostics, vaccine development and infection control
highlight its versatility and transformative potential in reshaping healthcare strategies.
By enabling targeted and controlled drug delivery, nanomaterial-based drug delivery
systems have the potential to revolutionize therapeutic interventions, minimizing side
effects and improving patient outcomes. Additionally, the integration of diagnostics
with therapeutic interventions through multifunctional nanoparticles facilitates real-time
monitoring of treatment responses, paving the way for personalized medicine
approaches. Furthermore, nanoparticle-based vaccine platforms offer promise for com­
bating infectious diseases and cancer by eliciting robust and durable immune responses.
The development of immunomodulatory nanoparticles further enhances the therapeutic
arsenal against immunosuppressive microenvironments in various disease settings. In
the realm of disease prevention, antimicrobial nanomaterials provide effective strategies
for infection control, while nanovaccines and prophylactic drug delivery systems offer
tailored solutions for mitigating the spread of infectious agents.

Note
1. Note, we offer only one (or two) references for a statement even though there are more in
the literature; the chosen are representative of those appropriate.

Disclosure statement
No potential conflict of interest was reported by the author(s).

References
00[1] Tang, L.; Wang, Y.; Li, J. The Graphene/Nucleic Acid Nanobiointerface. Chem. Soc. Rev.
2015, 44, 6954–6980. DOI: 10.1039/c4cs00519h.
00[2] Liu, X.; Wang, S. Three-Dimensional Nano-Biointerface as a New Platform for Guiding
Cell Fate. Chem. Soc. Rev. 2014, 43, 2385–2401. DOI: 10.1039/c3cs60419e.
00[3] Luo, S.; Mohamed Ali, E. A.; Tansil, N.; Yu, H.; Gao, S.; Kantchev, E.; Ying, J. Poly(3,4-
Ethylenedioxythiophene) (PEDOT) Nanobiointerfaces: Thin, Ultrasmooth, and
 JOURNAL OF MACROMOLECULAR SCIENCE, PART B 13

Functionalized PEDOT Films with in Vitro and in Vivo Biocompatibility. Langmuir

2008, 24, 8071–8077. DOI: 10.1021/la800333g.
00[4] Ishihara, K.; Takai, M. Bioinspired Interface for Nanobiodevices Based on Phospholipid
Polymer Chemistry. J. R Soc. Interface 2009, 6 Suppl 3, S279–S291. DOI: 10.1098/rsif.
2008.0335.
00[5] Tang, L.; Chang, H.; Liu, Y.; Li, J. Duplex DNA/Graphene Oxide Biointerface: From
Fundamental Understanding to Specific Enzymatic Effects. Adv. Funct. Mater. 2012, 22,
3083–3088. DOI: 10.1002/adfm.201102892.
00[6] Klefenz, H. Nanobiotechnology: From Molecules to Systems. Eng. Life Sci. 2004, 4, 211–
218. DOI: 10.1002/elsc.200402090.
00[7] Parameswaran, R.; Tian, B. Rational Design of Semiconductor Nanostructures for
Functional Subcellular Interfaces. Acc. Chem. Res. 2018, 51, 1014–1022. DOI: 10.1021/
acs.accounts.7b00555.
00[8] Fortina, P.; Kricka, L.; Surrey, S.; Grodzinski, P. Nanobiotechnology: The Promise and
Reality of New Approaches to Molecular Recognition. Trends Biotechnol. 2005, 23, 168–
173. DOI: 10.1016/J.TIBTECH.2005.02.007.
00[9] Matsusaki, M.; Akashi, M.; Takai, M.; Ishihara, K.; Ogino, T. Nanoscale Control of
Hetero-Biointerfaces. J. Surf. Sci. Soc. Jpn. 2009, 30, 193–201. DOI: 10.1380/jsssj.30.193.
0[10] Tian, B.; Lieber, C. Nanowired Bioelectric Interfaces. Chem. Rev. 2019, 119, 9136–9152.
DOI: 10.1021/acs.chemrev.8b00795.
0[11] Sun, Q.; Feng, J.; Han, D. Nanoimaging and Medically Functional Biointerfaces. Chin.
Sci. Bull. 2013, 58, 2449–2465. DOI: 10.1360/972012-1637.
0[12] Shende, P.; Wakade, V. S. Biointerface: A Nano-Modulated Way for Biological
Transportation. J. Drug Target 2020, 28, 456–467. DOI: 10.1080/1061186x.2020.1720218.
0[13] Pandey, S.; Bodas, D. High-Quality Quantum Dots for Multiplexed Bioimaging: A
Critical Review. Adv. Colloid Interface Sci. 2020, 278, 102137. DOI: 10.1016/j.cis.2020.
102137.
0[14] Mart�ınez Maestro, L.; Jacinto, C.; Rocha, U.; Carmen Iglesias-de la Cruz, M.; Sanz-
Rodriguez, F.; Juarranz, A.; Garc�ıa Sol�e, J.; Jaque, D. Optimum Quantum Dot Size for
Highly Efficient Fluorescence Bioimaging. J. Appl. Phys. 2012, 111, 023513. DOI: 10.
1063/1.3676251.
0[15] Hutter, E.; Maysinger, D. Gold Nanoparticles and Quantum Dots for Bioimaging.
Microsc. Res. Tech. 2011, 74, 592–604. DOI: 10.1002/jemt.20928.
0[16] Bhatia, S.; Narain, R.; Dutta, P. Multifunctional Gold Nanomaterials in Cancer
Theranostics: Opportunities and Challenges. Theranostics 2019, 9, 1337–1362. DOI: 10.
7150/thno.28464.
0[17] Chen, H.; Zhang, W.; Zhu, G.; Xie, J.; Chen, X. Rethinking Cancer Nanotheranostics.
Nat. Rev. Mater. 2017, 2, 17024. DOI: 10.1038/natrevmats.2017.24.
0[18] Wang, H.; Sun, D.; Zhao, N.; Luo, Y.; Lu, P. Multifunctional Magnetic Nanoparticles for
Cancer Theranostics: A Review on Recent Advances. Nanotechnology 2020, 31, 402001.
DOI: 10.1088/1361-6528/ab98bc.
0[19] Gao, J.; Gu, H.; Xu, B. Multifunctional Magnetic Nanoparticles: Design, Synthesis, and
Biomedical Applications. Acc. Chem. Res. 2009, 42, 1097–1107. DOI: 10.1021/ar9000026.
0[20] Zhao, Y.; Sultan, D.; Detering, L.; Cho, S.; Sun, G.; Pierce, R.; Wooley, K.; Liu, Y. Copper
Nanoclusters for Theranostic Applications. ACS Nano 2020, 14, 656–669. DOI: 10.1021/
acsnano.9b05752.
0[21] Lammers, T.; Aime, S.; Hennink, W.; Storm, G.; Kiessling, F. Theranostic Nanomedicine.
Acc. Chem. Res. 2011, 44, 1029–1038. DOI: 10.1021/ar200019c.
0[22] Mura, S.; Nicolas, J.; Couvreur, P. Stimuli-Responsive Nanocarriers for Drug Delivery.
Nat. Mater. 2013, 12, 991–1003. DOI: 10.1038/nmat3776.
0[23] Huang, X.; Jain, P.; El-Sayed, I.; El-Sayed, M. Gold Nanoparticles: Interesting Optical
Properties and Recent Applications in Cancer Diagnostics and Therapy. Nanomedicine
(London) 2007, 2, 681–693. DOI: 10.2217/17435889.2.5.681.
14 D. SINGH

0[24] Schroeder, K. L.; Goreham, R. V.; Nann, T. Graphene Quantum Dots for Theranostics
and Bioimaging. Pharm. Res. 2016, 33, 2337–2357. DOI: 10.1007/s11095-016-1937-x.
0[25] Yao, F.; Wang, Z. G.; Liu, S. L.; Wang, H.; Zhu, J.; He, R.; Yang, X.; Liu, X.; Wu, Q.;
Wu, J. K. Purified Fluorescent Nanohybrids Based on Quantum Dot–HER2–Antibody
for Breast Tumor Target Imaging. Talanta 2023, 260, 124560. DOI: 10.1016/j.talanta.
2023.124560.
0[26] Cheng, K. K.; Chan, P. S.; Fan, S.; Kwan, S. M.; Yeung, K. L.; W�ang, Y. X.; Chow, A. H.;
Wu, E. X.; Baum, L. Curcumin-Conjugated Magnetic Nanoparticles for Detecting
Amyloid Plaques in Alzheimer’s Disease Mice Using Magnetic Resonance Imaging
(MRI). Biomaterials 2015, 44, 155–172. DOI: 10.1016/j.biomaterials.2014.12.005.
0[27] Mirjalili, F.; Soltani, M.; Chen, P. Nanotechnology in Drug Delivery Systems. Int. J. Drug
Deliv. 2012, 4, 275–288.
0[28] Cortez-Jugo, C.; Czuba-Wojnilowicz, E.; Tan, A.; Caruso, F. A Focus on “Bio” in
Bio–Nanoscience: The Impact of Biological Factors on Nanomaterial Interactions. Adv.
Healthc. Mater. 2021, 10, e2100574. DOI: 10.1002/adhm.202100574.
0[29] Chen, D.; Wang, A. G.; Li, J. Interfacial Bioelectrochemistry: Fabrication, Properties and
Applications of Functional Nanostructured Biointerfaces. J. Phys. Chem. C 2007, 111,
2351–2367. DOI: 10.1021/jp065099w.
0[30] Liu, J.; Huang, Y.; Kumar, A.; Tan, A.; Jin, S.; Mozhi, A.; Liang, X. pH-Sensitive Nano-
Systems for Drug Delivery in Cancer Therapy. Biotechnol. Adv. 2014, 32, 693–710. DOI:
10.1016/j.biotechadv.2013.11.009.
0[31] Keles, E.; Song, Y.; Du, D.; Dong, W.; Lin, Y. Recent Progress in Nanomaterials for Gene
Delivery Applications. Biomater. Sci. 2016, 4, 1291–1309. DOI: 10.1039/c6bm00441e.
0[32] Zhang, P.; Liu, G.; Chen, X. Nanobiotechnology: Cell Membrane-Based Delivery Systems.
Nano Today 2017, 13, 7–9. DOI: 10.1016/j.nantod.2016.10.008.
0[33] Asil, S. M.; Ahlawat, J.; Barroso, G. G.; Narayan, M. Nanomaterial Based Drug Delivery
Systems for the Treatment of Neurodegenerative Diseases. Biomater. Sci. 2020, 8,
4109–4128. DOI: 10.1039/D0BM00809E.
0[34] Jacob, J.; Haponiuk, J.; Thomas, S.; Gopi, S. Biopolymer Based Nanomaterials in Drug
Delivery Systems: A Review. Mater. Today Chem. 2018, 9, 43–55. DOI: 10.1016/j.
mtchem.2018.05.002.
0[35] Maddiboyina, B.; Shanmugapriya, J.; Rasala, S.; Sivaraman, G. Bioinspired Nanomaterials
for Drug Delivery. In Bioinspired Materials Science and Engineering. Materials Research
Forum LLC, CRC Press: Millersville, PA, 2021; Vol. 111, pp 63–95. DOI: 10.21741/
9781644901571-3.
0[36] Iheaturu, N.; Diwe, I. V.; Daramola, O.; Sadiku, E. Polymeric Nanomaterials for Drug
Delivery. In: Materials Horizons: From Nature to Nanomaterials. Thakur, V. K., Eds.
The Netherlands: Springer International Publishing, 2019; Vol. 11, pp 143–155. DOI: 10.
1007/978-981-13-8063-1_11.
0[37] Sizikov, A. A.; Ringaci, A.; Dolotova, S. M.; Melikov, R.; Cherkasov, V. Biocompatible
and Highly Luminescent Quantum Dots for Bioimaging. Presented at the 2020
International Conference Laser Optics (ICLO). IEEE Explore, Petersburg, Russia, 2020.
pp. 1–4. DOI: 10.1109/ICLO48556.2020.9285901.
0[38] Peng, K.; Russell, S. Viral Vector Targeting. Curr. Opin. Biotechnol. 1999, 10, 454–457.
DOI: 10.1016/S0958-1669(99)00009-9.
0[39] Akinyelu, J.; Oladimeji, O.; Singh, M. Lactobionic Acid-Chitosan Functionalised Gold-
Coated Poly(Lactide-co-Glycolide) Nanoparticles for Hepatocyte Targeted Gene Delivery.
Adv. Nat. Sci: Nanosci. Nanotechnol. 2021, 11, 045017. DOI: 10.1088/2043-6254/abc9c3.
0[40] Zhang, C.; Yao, T.; Zheng, Y.; Li, Z.; Zhang, Q.; Zhang, L.; Zhou, D. Development of
Next Generation Adeno-Associated Viral Vectors Capable of Selective Tropism and
Efficient Gene Delivery. Biomaterials 2016, 80, 134–145. DOI: 10.1016/j.biomaterials.
2015.11.066.
 JOURNAL OF MACROMOLECULAR SCIENCE, PART B 15

0[41] Kasala, D.; Yoon, A.; Hong, J.; Kim, S. W.; Yun, C. Evolving Lessons on Nanomaterial-
Coated Viral Vectors for Local and Systemic Gene Therapy. Nanomedicine (London)
2016, 11, 1689–1713. DOI: 10.2217/nnm-2016-0060.
0[42] Bharali, D.; Klejbor, I.; Stachowiak, E.; Dutta, P.; Roy, I.; Kaur, N.; Bergey, E.; Prasad, P.;
Stachowiak, M. Organically Modified Silica Nanoparticles: A Nonviral Vector for in Vivo
Gene Delivery and Expression in the Brain. Proc. Natl. Acad. Sci. U S A 2005, 102,
11539–11544. DOI: 10.1073/pnas.0504926102.
0[43] Garbuzenko, O.; Mainelis, G.; Taratula, O.; Minko, T. Inhalation Treatment of Lung
Cancer: The Influence of Composition, Size and Shape of Nanocarriers on Their Lung
Accumulation and Retention. Cancer Biol. Med. 2014, 11, 44–55. DOI: 10.7497/j.issn.
2095-3941.2014.01.004.
0[44] Hubbell, J.; Chilkoti, A. Nanomaterials for Drug Delivery. Science 2012, 337, 303–305.
DOI: 10.1126/science.1219657.
0[45] Look, M.; Bandyopadhyay, A.; Blum, J.; Fahmy, T. Application of Nanotechnologies for
Improved Immune Response against Infectious Diseases in the Developing World. Adv.
Drug Deliv. Rev. 2010, 62, 378–393. DOI: 10.1016/j.addr.2009.11.011.
0[46] Yang, G.; Chen, S.; Zhang, J. Bioinspired and Biomimetic Nanotherapies for the
Treatment of Infectious Diseases. Front. Pharmacol. 2019, 10, 751–758. DOI: 10.3389/
fphar.2019.00751.
0[47] Gupta, A.; Mumtaz, S.; Li, C.-H.; Hussain, I.; Rotello, V. Combatting Antibiotic-Resistant
Bacteria Using Nanomaterials. Chem. Soc. Rev. 2019, 48, 415–427. DOI: 10.1039/
c7cs00748e.
0[48] Shi, J.; Kantoff, P. W.; Wooster, R.; Farokhzad, O. C. Cancer Nanomedicine: Progress,
Challenges and Opportunities. Nat. Rev. Cancer 2017, 17, 20–37. DOI: 10.1038/nrc.2016.
108.
0[49] Min, Y.; Caster, J. M.; Eblan, M. J.; Wang, A. Z. Clinical Translation of Nanomedicine.
Chem. Rev. 2015, 115, 11147–11190. DOI: 10.1021/acs.chemrev.5b00116.
0[50] Torchilin, V. P. Multifunctional and Stimuli-Sensitive Pharmaceutical Nanocarriers.
Eur. J. Pharm. Biopharm. 2009, 71, 431–444. DOI: 10.1016/j.ejpb.2008.09.026.
0[51] Bae, Y. H.; Park, K. Targeted Drug Delivery to Tumors: Myths, Reality and Possibility.
J. Control Release 2011, 153, 198–205. DOI: 10.1016/j.jconrel.2011.06.001.
0[52] Danhier, F.; Feron, O.; Pr�eat, V. To Exploit the Tumor Microenvironment: Passive and
Active Tumor Targeting of Nanocarriers for anti-Cancer Drug Delivery. J. Control
Release 2010, 148, 135–146. DOI: 10.1016/j.jconrel.2010.08.027.
0[53] Wagner, A. M.; Knipe, J.; Orive, G.; Peppas, N. Quantum Dots in Biomedical
Applications. Acta Biomater. 2019, 94, 44–63. DOI: 10.1016/J.ACTBIO.2019.05.022.
0[54] Zhao, P.; He, K.; Han, Y.; Zhang, Z.; Yu, M.; Wang, H.; Huang, Y.; Nie, Z.; Yao, S.
Near-Infrared Dual-Emission Quantum Dots-Gold Nanoclusters Nanohybrid via co-
Template Synthesis for Ratiometric Fluorescent Detection and Bioimaging of Ascorbic
Acid in Vitro and in Vivo. Anal. Chem. 2015, 87, 9998–10005. DOI: 10.1021/acs.anal­
chem.5b02614.
0[55] Beke, D.; Szekr�enyes, Z.; P�alfi, D.; R�
ona, G.; Balogh, I.; Ma�ak, P.; Katona, G.; Czig�any, Z.;
Kamar�as, K.; R� ozsa, B.; et al. Silicon Carbide Quantum Dots for Bioimaging. J. Mater.
Res. 2013, 28, 205–209. DOI: 10.1557/jmr.2012.296.
0[56] Younis, M. R.; He, G.; Lin, J.; Huang, P. Recent Advances on Graphene Quantum Dots
for Bioimaging Applications. Front. Chem. 2020, 8, 424–450. DOI: 10.3389/fchem.2020.
00424.
0[57] Patra, J.; Das, G.; Fraceto, L.; Campos, E.; Rodriguez-Torres, M. D. P.; Acosta-Torres, L.;
D�ıaz-Torres, L.; Grillo, R.; Swamy, M. K.; Sharma, S.; et al. Nano Based Drug Delivery
Systems: Recent Developments and Future Prospects. J. Nanobiotechnol. 2018, 16, 71.
DOI: 10.1186/s12951-018-0392-8.
0[58] Bianco, A.; Kostarelos, K.; Prato, M. Applications of Carbon Nanotubes in Drug
Delivery. Curr. Opin. Chem. Biol. 2005, 9, 674–679. DOI: 10.1016/J.CBPA.2005.10.005.
16 D. SINGH

0[59] Prasanna, A.; Pooja, R.; Suchithra, V.; Ravikumar, A.; Gupta, P.; Niranjan, V. Smart
Drug Delivery Systems for Cancer Treatment Using Nanomaterials. Mater. Today Proc.
2018, 5, 21047–21054. DOI: 10.1016/j.matpr.2018.06.498.
0[60] Eichhoff, A.; B€ orner, K.; Albrecht, B.; Sch€afer, W.; Baum, N.; Haag, F.; K€orbelin, J.;
Trepel, M.; Braren, I.; Grimm, D.; et al. Nanobody-Enhanced Targeting of AAV Gene
Therapy Vectors. Mol. Ther. Methods Clin. Dev. 2019, 15, 211–220. DOI: 10.1016/j.
omtm.2019.09.003.
0[61] Jov�cevska, I.; Muyldermans, S. The Therapeutic Potential of Nanobodies. BioDrugs 2019,
34, 11–26. DOI: 10.1007/s40259-019-00392-z.
0[62] Blanco, E.; Shen, H.; Ferrari, M. Principles of Nanoparticle Design for Overcoming
Biological Barriers to Drug Delivery. Nat. Biotechnol. 2015, 33, 941–951. DOI: 10.1038/
nbt.3330.
0[63] Wang, W.; Gao, D.; Liu, Y.; Zheng, G. Adenovirus as a Gene-Delivery Vehicle: Advances
in Viral Vector Design. Front. Biosci. 2020, 25, 151–166. DOI: 10.2741/4801.
0[64] Nayerossadat, N.; Maedeh, T.; Ali, P. Viral and Nonviral Delivery Systems for Gene
Delivery. Adv. Biomed. Res. 2012, 1, 27–31. DOI: 10.4103/2277-9175.100344.
0[65] Kay, M.; Glorioso, J.; Naldini, L. Viral Vectors for Gene Therapy: The Art of Turning
Infectious Agents into Vehicles of Therapeutics. Nat. Med. 2001, 7, 33–40. DOI: 10.1038/
83324.
0[66] Merten, O. W.; Hebben, M.; Bovolenta, C. Production of Lentiviral Vectors. Mol. Ther.
Methods Clin. Dev. 2016, 3, 16017. DOI: 10.1038/mtm.2016.17.
0[67] Verdera, H. C.; Kuranda, K.; Mingozzi, F. AAV Vector Immunogenicity in Humans:
A Long Journey to Successful Gene Transfer. Mol. Ther. 2020, 28, 723–746. DOI: 10.
1016/j.ymthe.2019.12.016.
0[68] Mingozzi, F.; High, K. Immune Responses to AAV in Clinical Trials. Curr. Gene Ther.
2011, 11, 321–330. DOI: 10.2174/156652311796150408.
0[69] Thomas, C.; Ehrhardt, A.; Kay, M. Progress and Problems with the Use of Viral Vectors
for Gene Therapy. Nat. Rev. Genet. 2003, 4, 346–358. DOI: 10.1038/nrg1066.
0[70] Balakrishnan, B.; Jayandharan, G. R. Basic Biology of Adeno-Associated Virus (AAV)
Vectors Used in Gene Therapy. Curr. Gene Ther. 2014, 14, 86–100. DOI: 10.2174/
1566523214666140508144426.
0[71] Huang, X.; Jain, P. K.; El-Sayed, I. H.; El-Sayed, M. A. Plasmonic Photothermal Therapy
(PPTT) Using Gold Nanoparticles. Lasers Med. Sci. 2008, 23, 217–228. DOI: 10.1007/
s10103-007-0470-x.
0[72] Jang, B.; Park, J. Y.; Tung, C. H.; Kim, I. H.; Choi, Y. Gold Nanorod–Photosensitizer
Complex for near-Infrared Fluorescence Imaging and Photodynamic/Photothermal
Therapy in Vivo. ACS Nano 2011, 5, 1086–1094. DOI: 10.1021/nn103098c.
0[73] Robinson, J. T.; Tabakman, S. M.; Liang, Y.; Wang, H.; Casalongue, H. S.; Vinh, D.; Dai,
H. Ultrasmall Reduced Graphene Oxide with High near-Infrared Absorbance for
Photothermal Therapy. J. Am. Chem. Soc. 2011, 133, 6825–6831. DOI: 10.1021/
ja2010175.
0[74] Mody, N.; Tekade, R.; Mehra, N.; Chopdey, P.; Jain, N. Dendrimer, Liposomes, Carbon
Nanotubes and PLGA Nanoparticles: One Platform Assessment of Drug Delivery
Potential. AAPS PharmSciTech 2014, 15, 388–399. DOI: 10.1208/s12249-014-0073-3.
0[75] Ogunsona, E. O.; Muthuraj, R.; Ojogbo, E.; Valerio, O.; Mekonnen, T. Engineered
Nanomaterials for Antimicrobial Applications: A Review. Appl. Mater. Today 2020, 18,
100473. DOI: 10.1016/j.apmt.2019.100473.
0[76] Azizi-Lalabadi, M.; Hashemi, H.; Feng, J.; Jafari, S. M. Carbon Nanomaterials against
Pathogens; the Antimicrobial Activity of Carbon Nanotubes, Graphene/Graphene Oxide,
Fullerenes, and Their Nanocomposites. Adv. Colloid Interface Sci. 2020, 284, 102250.
DOI: 10.1016/j.cis.2020.102250.
0[77] Hemeg, H. A. Nanomaterials for Alternative Antibacterial Therapy. Int. J. Nanomed.
2017, 12, 8211–8225. DOI: 10.2147/IJN.S132163.
 JOURNAL OF MACROMOLECULAR SCIENCE, PART B 17

0[78] Graves, J. L.; Thomas, M. D.; Ewunkem, J. A. Antimicrobial Nanomaterials: Why

Evolution Matters. Nanomaterials (Basel)2017, 7, 283–287. DOI: 10.3390/nano7100283.
0[79] Svenson, S. What Nanomedicine in the Clinic Right Now Really Forms Nanoparticles?
Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2014, 6, 125–135. DOI: 10.1002/wnan.
1257.
0[80] Lombardo, D.; Calandra, P.; Bellocco, E.; Lagan�a, G.; Barreca, D.; Magaz� u, S.;
Wanderlingh, U.; Kiselev, M. Effect of Anionic and Cationic Polyamidoamine (PAMAM)
Dendrimers on a Model Lipid Membrane. Biochim. Biophys. Acta 2016, 1858, 2769–
2777. DOI: 10.1016/j.bbamem.2016.08.001.
0[81] Blecher, K.; Nasir, A.; Friedman, A. The Growing Role of Nanotechnology in Combating
Infectious Disease. Virulence 2011, 2, 395–401. DOI: 10.4161/viru.2.5.17035.
0[82] Feng, X.; Xu, W.; Li, Z.; Song, W.; Ding, J.; Chen, X. Immunomodulatory Nanosystems.
Adv. Sci. (Weinh.) 2019, 6, 1900101. DOI: 10.1002/advs.201900101.
0[83] Mart�ın-Contreras, M.; Navarro-Marchal, S.; Peula-Garc�ıa, J. M.; J� odar-Reyes, A. B.
Progress and Hurdles of Therapeutic Nanosystems against Cancer. Pharmaceutics 2022,
14, 388–399. DOI: 10.3390/pharmaceutics14020388.
0[84] Ross, K.; Brenza, T. M.; Binnebose, A. M.; Phanse, Y.; Kanthasamy, A.; Gendelman, H.;
Salem, A.; Bartholomay, L.; Bellaire, B.; Narasimhan, B. Nano-Enabled Delivery of
Diverse Payloads across Complex Biological Barriers. J. Control Release 2015, 219, 548–
559. DOI: 10.1016/j.jconrel.2015.08.039.
0[85] Lim, J.-W.; Ahn, Y.-R.; Park, G.; Kim, H.-O.; Haam, S. Application of Nanomaterials as
an Advanced Strategy for the Diagnosis, Prevention, and Treatment of Viral Diseases.
Pharmaceutics 2021, 13, 1570–1579. DOI: 10.3390/pharmaceutics13101570.
0[86] Guerra, G. European Regulatory Issues in Nanomedicine. Nanoethics 2008, 2, 87–97.
DOI: 10.1007/s11569-008-0031-1.
0[87] Bruce, D. Ethical and Social Issues in Nanobiotechnologies: Nano2Life Provides a
European Ethical ‘Think Tank’for Research in Biology at the Nanoscale. EMBO Rep.
2006, 7, 754–758. DOI: 10.1038/sj.embor.7400762.
0[88] Brownsword, R. Regulating Nanomedicine—the Smallest of Our Concerns? Nanoethics
2008, 2, 73–86. DOI: 10.1007/s11569-008-0030-2.
0[89] Rudramurthy, G. R.; Swamy, M. K.; Sinniah, U.; Ghasemzadeh, A. Nanoparticles:
Alternatives against Drug-Resistant Pathogenic Microbes. Molecules 2016, 21, 836–844.
DOI: 10.3390/molecules21070836.
0[90] Feng, Y.; Liu, L.; Zhang, J.; Aslan, H.; Dong, M. Photoactive Antimicrobial
Nanomaterials. J. Mater. Chem. B 2017, 5, 8631–8652. DOI: 10.1039/C7TB01860F.
0[91] Reshma, V. G.; Syama, S.; Sruthi, S.; Reshma, S.; Remya, N.; Mohanan, P. Engineered
Nanoparticles with Antimicrobial Property. Curr. Drug Metab. 2017, 18, 1040–1054.
DOI: 10.2174/1389200218666170925122201.
0[92] Marrani, D. Nanotechnologies and Novel Foods in European Law. Nanoethics 2013, 7,
177–188. DOI: 10.1007/s11569-013-0176-4.
0[93] Preston, C.; Sheinin, M. Y.; Sproat, D.; Swarup, V. The Novelty of Nano and the
Regulatory Challenge of Newness. Nanoethics 2010, 4, 13–26. DOI: 10.1007/s11569-010-
0083-x.
0[94] Sainz, V.; Conniot, J.; Matos, A. I.; Peres, C.; Zupancic, E.; Moura, L.; Silva, L. C.;
Florindo, H. F.; Gaspar, R. S. Regulatory Aspects on Nanomedicines. Biochem. Biophys.
Res. Commun. 2015, 468, 504–510. DOI: 10.1016/j.bbrc.2015.08.023.
0[95] Iavicoli, I.; Leso, V.; Beezhold, D.; Shvedova, A. Nanotechnology in Agriculture:
Opportunities, Toxicological Implications, and Occupational Risks. Toxicol. Appl.
Pharmacol. 2017, 329, 96–111. DOI: 10.1016/j.taap.2017.05.025.
0[96] Singh, N.; Manshian, B.; Jenkins, G.; Griffiths, S. M.; Williams, P.; Maffeis, T.; Wright,
C.; Doak, S. NanoGenotoxicology: The DNA Damaging Potential of Engineered
Nanomaterials. Biomaterials 2009, 30, 3891–3914. DOI: 10.1016/j.biomaterials.2009.04.009.
0[97] Paradise, J.; Wolf, S.; Ramachandran, G.; Kokkoli, E.; Hall, R.; Kuzma, J. Developing
Oversight Frameworks for Nanobiotechnology. Telecom Reg. Ind. eJ 2008, 9, 187–191.
18 D. SINGH

0[98] Le Roux, R. A Matter of Accuracy. Nanobiochips in Diagnostics and in Research: Ethical

Issues as Value Trade-Offs. Sci. Eng. Ethics 2015, 21, 343–358. DOI: 10.1007/s11948-014-
9550-z.
0[99] Fadeel, B.; Feliu, N.; Vogt, C.; Abdelmonem, A. M.; Parak, W. J. Bridge over Troubled
Waters: Understanding the Synthetic and Biological Identities of Engineered
Nanomaterials to Advance Their Environmental and Biomedical Applications. ACS Nano
2013, 7, 9147–9155. DOI: 10.1021/nn4034477.
[100] Park, B.; Donaldson, K.; Duffin, R.; Tran, L.; Fernandez, T.; Judson, R.; Newhouse, M.;
Miller, B.; Stone, V. The Role of Oxidative Stress in Determining the Biocompatibility of
Nanomaterials. Toxicology 2011, 279, 99–118. DOI: 10.1016/j.tox.2010.10.011.
[101] Petersen, E. J.; Henry, T. B. Methodological Considerations for Testing the Ecotoxicity of
Carbon Nanotubes and Fullerenes: Review. Environ. Toxicol. Chem. 2012, 31, 60–72.
DOI: 10.1002/etc.710.
[102] Fadeel, B.; Pietroiusti, A.; Shvedova, A. A. Adverse Effects of Engineered Nanomaterials:
Exposure, Toxicology, and Impact on Human Health. The Neitherlands: Elsevier Inc,
2017; pp 23–45 DOI: 10.1016/C2014-0-03333-1.
[103] Silva, G. A. Ethical and Regulatory Issues in the Clinical Translation of Nanotechnology.
Methods Mol. Biol. 2011, 726, 487–501. DOI: 10.1007/978-1-4614-0529-9_27.