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12 PEGylated Nanocarriers forDiagnostic Applications
Fig. 12.1 Prevention of
opsonization by surface
modication of
nanocarriers with PEG
347
binding, non-covalent entrapment, or adsorption of PEG onto a product and is a
common term for PEG modication (Van Vlerken etal. 2007).
A highly effective strategy for enhancing therapeutic drug systemic distribution
is the PEGylation of nanoparticles (NPs). PEGylation of NPs has also been
employed as a method to cross-extracellular barriers related to alternative administration methods, such as distribution to the mucosa or delivery to the brain. PEG
coatings will undoubtedly remain an integral component in the design of NPs for
drug and gene delivery applications, enabling more research to understand how the
characteristics of PEG coating affect NPs biodistribution and removal from the body.
As more NP-based products are being used in the clinical setting, it is unclear
what role the emerging PEG alternatives will play. However, further research into
the potential immunogenic properties of PEG coatings as a function of molecular
weight, functional group, surface density, NPs core properties, dosing frequency,
etc., will undoubtedly result in more effective products (Suk etal. 2016).
12.1.1 Modification ofthePEG Surface
andLong-Circulation Properties
The typical structure of PEG is HO-(CH2CH2O)n-CH2CH2-OH, which includes a
chemically inert polyether backbone and terminal hydroxyl groups that can be triggered for conjugation to various polymers and medicinal products. Poloxamers and
poloxamines, which are amphiphilic block co-polymers made of blocks of hydrophilic PEG and hydrophobic polypropylene oxide (PPO), are additionally PEG
derivatives frequently used for surface adsorption or entrapment modication.
Covalent methods, such as grafting PEG chains onto the surface of the polymeric
NPs, or co-polymers, in which PEG is covalently bonded to another type of polymer, can modify the surface of the NPs. PEG has the benets of being non-toxic and
non-immunogenic, which led to the FDA of the United States approving it for use
in individuals internally, a listing of inactive substances for parenteral and oral use,
as well. Considering PEG is not biodegradable, it is available in a wide range of
molecular weights up to several million daltons, which affects the rate at which the
body can eliminate it.
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N. Gupta et al.
PEG chains with a larger molecular weight shift from urine to fecal excretion.
The protective (stealth) action of PEG is mainly due to the formation of a dense,
hydrophilic cloud of long exible chains on the surface of the colloidal particles that
reduces the hydrophobic interactions with the RES.The tethered and/or chemically
anchored PEG chains can undergo spatial conformations, thus preventing the opsonization of particles by the macrophages of the RES, which leads to preferential
accumulation in the liver and spleen. PEG surface modication, therefore, enhances
the circulation time of molecules and colloidal particles in the blood (Van Vlerken
etal. 2007).
Today, PEGylation is crucial for imaging and diagnosing different body tissues.
Macromolecular chelators such as polymers, antibodies, and recognition proteins
are becoming more popular among chelators. PEGylation extends the period that
paramagnetic chelates remain in the body. These chelates will then be eliminated
from the body at slower rates through the kidney or liver than unmodied molecules, providing magnetic resonance to produce accurate images. PEG also serves
as a linker between the targeting and diagnostic moieties, which signicantly
impacts the biodistribution pattern of radiodiagnostics. PEG might assist in collecting more precise pictures in the case of protein-targeted diagnostics by reducing
background noise brought on by nonspecic protein–protein interaction (Veronese
and Pasut 2005).
To increase the effectiveness of drug and gene delivery to target cells and tissues,
PEG is frequently used to coat the surface of NPs, a process known as “PEGylation.”
The length of the systemic circulation is increased by PEG coatings on NPs, which
protect the surface from opsonization, aggregation, and phagocytosis.
Systemically delivered medicines must circulate in the bloodstream for as long
as possible to reach target tissues at sufcient concentrations. However, proteins
and peptides rapidly break down and are removed from the blood; therefore, methods for prolonging circulation duration are required. One such way is to coat the
therapeutic’s surface with an inert polymer that prevents interactions with bloodstream constituents and gives it “stealth” qualities. Due to its long history of safety
in human usage and FDA classication as Generally Regarded as Safe (GRAS),
PEG is the most commonly utilized “stealth” polymer in the drug delivery industry
(Li and Huang 2010).
Branched PEGs may provide steric repulsion due to the attachment of neighboring PEG molecules, resulting in empty spaces on the surface, just enough to attract
the nonspecic binding of opsonin proteins. These molecular weights of PEG have
been reported to be between 1500 and 5000. To get the highest stealth qualities, a
high density of short-chain PEG molecules is required, yet chains that are too short
may be too rigid to give the necessary exibility (Karakoti etal. 2011).
12.1.2 Current Market Scenario
Many PEG-based medications have been developed, and a number of these have
gained market acceptance. Due to vast clinical expertise, it has become possible to
12 PEGylated Nanocarriers forDiagnostic Applications
349
synthesize PEG prodrug conjugates with increased therapeutic efcacy while minimizing systemic toxicity. PEGylated products, such as PEGvisomant and certolizumab PEGol, demonstrated that PEGylated forms can be commercialized
independently of the past commercialization of their non-PEGylated counterparts.
In contrast, PEGylated drugs, such as PEGinterferon and PEGlgrastim, have
proven their cost-effectiveness in the market. The market for therapeutic PEGylated
proteins appears to have strong long-term potential. Because of its enormous clinical advantages, PEGylation is fundamental in delivering and targeting drugs and
other bioactives. PEGylation is essential for achieving cellular targetability
(Banerjee etal. 2012).
Few well-known PEGylated products in the market include PEG-interferon α-2a,
PEG-Intron (PEG-interferon alpha-2b) for hepatitis (Herndon etal. 2012), Somavert
(PEG-human growth hormone receptor antagonist) for acromegaly (Alconcel etal.
2011), Cimzia (certolizumabPEGol, PEGylated antihuman TNF-alpha Fab) for
rheumatoid arthritis (Lang 2008), Neulasta (PEGlgrastim, PEG-recombinant
human granulocyte colony stimulating factor analogue) for neutropenia associated
with cancer chemotherapy (Bence etal. 2002), PEG-erythropoietin (EPO) for anemia (Rubio 2015), Adagen (PEG-adenosine deaminase) for immunodeciency
(Booth and Gaspar 2009), PEG-Hirudin for thrombosis, and Oncaspar (PEG asparaginase) for cancer treatment (Dinndorf etal. 2007).
More than 20 PEGylated nanocarriers have received clinical approval from the
US FDA to date, including Doxil and Macugen, which are essential in managing
cancer and neovascular age-related macular degeneration (Shi etal. 2021).
12.1.3 Ideal Properties ofPEGylated Nanocarriers
forDiagnostic Applications
PEG is an aqueous, safe, non-toxic, non-immunogenic, and non-antigenic polymer
that is FDA-approved for human use. They are miscible with glycols, soluble in
water, alcohol, acetone, and chloroform, and insoluble in ether. Due to its purported
“stealth” qualities and biocompatibility, polyethylene glycol is frequently used in
pharmaceutical delivery. The PEG-drug conjugates have several benets, including
an extended residence in the body, delaying renal clearance, a reduced breakdown
rate by metabolic enzymes, and a decreased level of protein immunogenicity. The
viscosity of PEG solution with lower molecular weight is low and increases with the
increase of molecular weight. PEG’s distinctive stability against oxidation, reduction, and decomposition by acids, bases, relatively high temperatures, hydrogen
peroxide, and sodium borohydride distinguishes it from other materials. Because
PEG contains both hydrophilic and hydrophobic groups, it is a preferred solvent for
green synthesis. Because of its capacity to exhibit phase separation under regulated
conditions. The stealth features offered by PEG coatings have enhanced the enormous potential of nanoparticles in therapy, diagnostic imaging, treatment, and disease prevention (Karakoti etal. 2011).
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N. Gupta et al.
Nanoparticles with PEG coatings prevent surface aggregation, opsonization, and
phagocytosis, extending circulation duration. Doxil, the rst PEGylated NPs product to receive FDA approval, was introduced in 1995. With a drug half-life of 72h
and a circulation half-life of 36h, Doxil “Stealth” liposomes enhanced doxorubicin
bioavailability about 90-fold at 1 week after injection compared to free drug
(Working etal. 1994).
The therapeutic effectiveness of systemic chemotherapy is insufcient, and the
systemic toxicity restricts the dosages of injectable drugs, thus reducing their therapeutic efcacy. Creating a revolutionary system that permits early diagnosis and
tailored therapy to address these shortcomings in present diagnostic and therapeutic
techniques is essential.
12.2 PEGylated Nanocarriers inDiagnostic Applications
Recently, nanotechnology has drawn attention for its novel cancer diagnostic and
therapeutic tool. These alternatives have been used to overcome the challenges that
traditional diagnostic and therapeutic approaches offer. These difculties include
toxicity, rapid drug release, and non-specicity. According to research done over the
years, nanocarriers improve the bioavailability, specicity, and accumulation of
medications at the target location. Their easily adjustable physical and chemical
features can be attributed to these advancements. They are frequently altered in size
and surface texture to improve their accumulation at the target areas and overall
targeting capabilities. Nanocarriers are good candidates for uorescence-guided
surgery and imaging methods due to their impressive uorescent characteristics.
Biomimetic NPs, which effectively interact with complicated biological systems
and imitate the functions of biological components, are another potential class of
NPs (Zhang etal. 2020).
Researchers are examining nanotechnology-based tools and techniques as viable
potential for the early diagnosis and treatment of cancer. Numerous studies have
been done on enhancing targeted drug delivery and imaging while preserving efcacy. PEGylated nanocarriers have been utilized in recent times for the diagnosis
and imaging of many diseases, including tumors. PEGylated magnetic NPs demonstrating magnetic characteristics are frequently used in magnetic targeting, magnetic heating, and MRI contrast enhancement. Long-circulating NPs required for
MRI and other theranostic applications are well-coated with PEGs (Illés etal. 2018).
A diagnostic tool that can characterize EPR is vital from a diagnostic standpoint.
PEGylated NPs may be used to monitor drug release and long-term pharmacological efcacy, visualize and quantify biodistribution, and target site accumulation of
NPs. Nanoparticles help characterize tumor angiogenesis, and very tiny NPs (less
than 5 nm) can be utilized for molecular diagnostics for extravascular targets
(Baetke etal. 2015).
The physicochemical characteristics of NPs make them suitable delivery systems
for delivering drugs to brain tumors. The core or the surface of NPs can be coated
with molecules, such as contrast agents or medications. As MRI contrast agents,
12 PEGylated Nanocarriers forDiagnostic Applications
351
numerous NPs have been developed with or without an organic material shell-like
polyethylene glycol. NPs could be designed for imaging specic cell subpopulations, like endothelial cells or stem cells. NPs may advance the diagnosis, surgical
treatment, and adjuvant therapy of brain tumors. NPs-based MRI contrast agents
have the potential to make tumor areas visible that would not have been seen with
conventional MRI, particularly at the tumor–brain interface (Cho etal. 2010).
Systemic chemotherapy exhibits an unfavorable biodistribution of anticancer
medicines after systemic delivery, resulting in severe side effects, and has limited
therapeutic efcacy. Additionally, systemic toxicity restricts the dosages of injectable drugs, thereby lowering their therapeutic efcacy. Creating a revolutionary system that permits early diagnosis and tailored therapy to address these shortcomings
in present diagnostic and therapeutic approaches is vital. The development of a
method that allows early identication and focused treatment to enhance current
procedures that have a high failure rate of colon cancer leading to metastases is
crucial for improved management of colon cancer.
Colon tumors were successfully examined utilizing an near-infrared uorescence (NIRF) imaging technique using a theranostic carrier system based on
PEGylated hyaluronic acid NPs bearing NIRF imaging dye. Because of their
remarkable tumor-targeting abilities, they demonstrated signicant inhibition of
tumor growth with less systemic toxicity (Choi etal. 2012).
12.2.1 PEGylated Iron Oxide Nanoparticles
Polyethylene glycol has been extensively used on various nanoparticle systems to
increase surface hydrophilicity and improve circulation half-life by decreasing
interactions with blood proteins and mononuclear phagocyte system (MPS) cells.
The use of PEGylated iron oxide NP ferrouids in invivo biomedical applications
such as magnetic imaging resonance (MRI) contrast enhancement and cancer therapy by hyperthermia and/or targeted drug delivery is currently the subject of
research. The magnetic characteristics of NPs could be utilized for drug delivery to
improve the antitumor efcacy and lessen the systemic side effects of anticancer
medications. Loaded PEGylated iron oxide NPs may be held in a cancer site and
afterward released the drug there if an external localized magnetic eld is applied.
The surface of iron oxide NPs has been transformed using PEG, which has been
proven to increase biocompatibility and blood circulation rates. PEG surface coating is utilized to prevent plasma adsorption and escape from the MPS (Shan
etal. 2009).
Gadolinium, superparamagnetic iron oxides, ultrasmall (5–10nm) superparamagnetic iron oxides, gadolinium-doped carbon nanotubes, quantum dots embedded paramagnetic micelles, and soft NPs are currently excellent magnetic contrast
agents in the research eld. With their magnetic properties and contrast, PEGylated
iron oxide NPs have already succeeded in biomedical areas such as diagnostics as
a probe (MRI scanning) for discovering diseases or issues within the brain, cardiovascular system, liver, blood arteries, and other essential organs. PEGylated
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N. Gupta et al.
iron oxide NPs have also been designed with advancements for carrying out multiple operations in single-stage imaging. In recent times, PEGylated iron oxide
NP-based nanohybrids were modied for partial thromboplastin time (PTT) and
hyperthermia, where even small concentrations can effectively increase heat generation at the tumor site and be employed for cellular treatments (Vallabani and
Singh 2018).
PEGylated iron oxide nanoparticles with specic surface chemical characteristics have been widely exploited for several biological applications, including cell
separation, tissue healing, targeted drug delivery, hyperthermia, and MRI contrast
enhancement. Due to their low toxicity, size-dependent superparamagnetism, and
biocompatibility with cells and tissue, superparamagnetic nature, PEGylated iron
oxide NPs may, therefore, be able to increase contrast in MRI images more effectively than typical paramagnetic Gadolinium (Gd)-based contrast agents.
Additionally, leaky vasculatures near tumors cause PEGylated iron oxide NPs with
an appropriate particle size to accumulate in tumor sites through the enhanced permeability and retention (EPR) effect. Developing PEGylated iron oxide NPs with
controlled size and shape-restricted size distribution is preferable to gain advantage
from their high-quality and regular imaging property in MRI and precise tumor
targeting (Yue-Jian etal. 2010).
PEGylated iron oxide NPs can replace the currently utilized gadolinium-based
contrast agents in MRI, which have demonstrated poor blood lifetime and low
proton relaxation efciency. These limitations have led to greater administration
doses, increasing human and environmental toxicity. Results indicate that these
particles may be used for therapeutic applications and longitudinal imaging studies
due to their high specic absorption rate (SAR) values. These biocompatible NPs
are a potent tool for biomedical applications, primarily because of the current
interest in non-invasive diagnostic assays based on real-time and long-term tracking and monitoring of tagged cells (i.e., tumor-related macrophages) (LazaroCarrillo et al. 2020). There are many different biomedical and bioengineering
applications for PEGylated iron oxide NPs, which belong to the family of magnetic
materials known as ferrimagnetic materials. There are different types of iron oxidebased NPs like maghemite (y-Fe2O3), magnetite (Fe3O4), and mixed ferrites
(MFe2O4), where M=Co, Mn, Ni, or Zn). PEGylated iron oxide NPs are produced
after surface modication. They can be used for magnetic resonance imaging,
magnetic particle imaging (MPI), targeted delivery of drugs, proteins, antibodies,
and nucleic acids, separation of biomolecules, hyperthermia, biosensing, and tissue repair. These current exhaustive applications are brought about by magnetic
characteristics and the fact that they may be synthesized in various forms and sizes.
When exposed to an external magnetic eld, superparamagnetic iron oxide
nanoparticles have signicant magnetic moments, and even when the magnetic
eld is removed, there is no longer any magnetic moment. In preclinical and clinical trials, many iron oxide NPs have been examined, and a number of them have
been commercialized.
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353
12.2.2 PEGylated Magnetic Nano Assemblies inDiagnosis
Magnetic nanocrystals made in an organic phase can be employed as contrast agents
because of their well-dened crystal structures and excellent magnetic sensitivity.
To increase their colloidal stability in the aqueous phase, additional surface modication with a hydrophilic layer, for example, PEG, is needed because they are disseminated in the organic phase. PEG has a high hydrophilicity, a low cytotoxicity,
and a high cell permeability. Specically, it helps reduce nonspecic interactions
with serum proteins by creating hydrogen bonds with water molecules, which
extends the duration that the substance is in circulation in the blood. For PEG-based
materials, there are two primary surface modication techniques. The rst one is the
exchange technique, in which the hydrophobic ligand on the magnetic nanocrystal
(MNC) surface is replaced with PEG at elevated temperatures, and the second technique is the addition technique, in which a hydrophobic MNC’s surface is covered
with the emulsion technique using a PEG-based amphiphilic polymer as a surfactant (Fig.12.2).
Using this addition technique, it is possible to load MNCs, uorescent materials,
and drugs together to create a multifunctional nanocomposite. It is challenging to
obtain constantly sized NPs, particularly nanoclusters. Because it also triggers the
transition between the super magnetic–ferrimagnetic transitions, growing the size
of MNCs to increase the saturation magnetization has limitations. Instead, it has
been suggested that creating magnetic nanoclusters successfully maintains superparamagnetic behavior with high magnetization.
Due to their high magnetic susceptibility, low coercive force, and high magnetic
characteristics, magnetic NPs made up of several single MNCs are very appealing.
Due to the PEG molecules on the particle surface (PEGylation effect), the PEGylated
MNs displayed better durability in an aqueous phase for a longer period of time than
those of a commercial MRI contrast agent, as well as an appropriate MRI contrast
Fig. 12.2 An illustration of a magnetic nanoparticle structure for targeting ligands, uorophores,
and responsive elements
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N. Gupta et al.
effect due to the magnetic clustering effect. Additionally, invivo tests conrm that
PEGylated MNCs have a potential value as MRI agents for cancer diagnosis (Kang
etal. 2019). An external magnetic eld can inuence magnetic NPs, indicating their
ability to be site-specic. MNPs are an excellent choice for the simultaneous delivery of diagnostic and treatment, commonly known as theranostics; due to their
imaging capabilities and magnetic characteristics, MNPs have a higher theranostic
potential than liposomes or other polymer-based nanoparticles. Owing to their
capacity to be simultaneously directed, visualized, and heated by external magnetic
elds, MNPs are useful in theranostics (Alromi etal. 2021). Magnetic nanoparticles
are being developed and employed in magnetic resonance imaging as contrastenhancing agents for diagnosing a wide range of ailments, including cancer, cardiovascular disease, and neurological disorders.
Magnetic NPs that have been radioactively labeled have been shown to be highly
effective at diagnosing cancer. Compared to conventional imaging methods, it has
few key advantages. Due to the EPR effect, magnetic NPs labelled with radioactive
tracers have precision targeting; they also have a high surface-to-volume ratio,
enabling the use of high-density radioactive labels; and they are capable of complementary multimodal imaging, such as integrated imaging using various radionuclide nanoparticles.
Magnetic uorescent nanocomposites that are superparamagnetic and uorescent have been developed by integrating magnetic NPs with uorescent elements.
The efciency of cell imaging is signicantly increased when the magnetic uorescent nanocomposites are introduced to living cells because the uorescence can be
monitored and programmed to be enriched at the desired area when an external
magnetic eld is applied.
In addition to having the general features of NPs, magnetic NPs also possess
magnetic capabilities, which have recently attracted the attention of researchers in
the eld of nanomedicine. Due to their special characteristics, magnetics are extensively employed in biomedicine, drug-gene delivery, magnetic resonance imaging,
molecular probes, tumor detection, tumor therapy, and other domains. Magnetic
NPs will be utilized more frequently in tumor diagnosis and treatment as nanotechnology advances (Bian etal. 2021).
12.2.3 PEGylated Quantum Dots inTargeted Tissue Imaging
PEGylated quantum dots (QDs) are uorescent NPs, distinguished by their extraordinary optical characteristics, including strong uorescence emission, photostability, a compact emission spectrum, and a wide excitation wavelength. They are an
intriguing option for applications involving bioimaging due to such features. The
PEG coating helps them escape plasma protein adsorption and RES clearance,
which prolongs the blood circulation of quantum dots in the body and increases the
possibility that they will reach to their target area successfully. PEGylated QDs is
currently a dynamic delivery system for diagnostic applications (Fig.12.3).
12 PEGylated Nanocarriers forDiagnostic Applications
Fig. 12.3 Targeting of quantum dots
355
Long-term dynamic imaging is a perfect application for PEGylated QDs because
of their optical characteristics, specically their capacity to emit uorescence in the
near-infrared (NIR) range and their resistance to photobleaching. As a result, they
could be utilized in uorescence-guided surgery (FGS) to speed up tumor removal
and produce negative surgical margins and therefore enhancing the prognosis of a
patient. In surgical oncology, FGS is a real-time intraoperative procedure, which is
designed to highlight tumors during surgical resection to speed up tumor excision
and provide negative tumor margins. The prognosis of a patient must be improved
by complete tumor excision with negative margins. Additionally, PEGylated QDs
have the ability to generate uorescence in the near-infrared spectrum, which is of
signicant relevance to uorescence-guided surgery (Dirheimer etal. 2022).
They provide enhanced uorescence intensity, superior photobleaching resistance, size-tunable light emission, and the capacity to generate different uorescent
colors from a single excitation source. The optimum surface for coupling with a
range of targets, such as antibodies, peptides, and several other small molecules, is
offered by QDs. They might thus present effective alternatives to the more sensitive
and focused cancer molecular targeting and bioimaging detection methods currently
in use. Cancer imaging has evolved greatly since Gao intravenously administered
PEG-coated QDs functionalized with antibodies to prostate-specic membrane
antigen. Furthermore, the ability to resist bleaching for extended periods enables the
collection of sharp, well-contrasted images that are particularly helpful for 3D optical sectioning of tumors and the environment around them because bleaching of
uorophores hinders the accurate reconstruction of 3D structures.
Additionally, their long-term stability, excellent brightness, wider and continuous excitation spectrum, and deep penetration make them the perfect choice for
invivo cancer diagnostics and bio-imaging. Some of the goals of creating new and
improved cancer diagnostics and imaging probes have already been realized because
of the rapid advancement of QDs technology. The active targeting of tumors is now
achievable due to their characteristics and effective conjugation with biomolecules.
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N. Gupta et al.
Despite the potential and large application of QDs in cancer imaging and detection
to date, there are still obstacles to be cleared in terms of improving specicity,
enhancing sensitivity, and reducing QDs toxicity before clinical applications may
advance (Liang etal. 2021).
Aptamer-conjugated PEGylated QDs is recent advancement for targeting epidermal growth factor receptor variant III for uorescence imaging of glioma. In glioma
patients, the degree of resection plays a substantial predictive role. However,
because tumors are naturally inltrative, it is challenging to identify the maximal
safe resection level. Recently, FGS, a novel technique for safely removing gliomas,
has emerged. PEGylated QDs have a number of exceptional benets, including
chemical stability, broad absorption with narrow emission spectra, high quantum
uorescence yield, and water solubility. QDs have signicantly increased biocompatibility when their shell is made of ZnS and coated with PEG.Additionally, the
PEG coating helps them to evade plasma protein adsorption and RES clearance,
which increases the likelihood that they will reach their intended area.
One of the most well-known near-infrared imaging probes was made using
PEGylated Silver Sulphide QDs with special optical properties. They showed muchimproved blood ow and tumor accumulation invivo when compared to the original ones, making them great candidates for use as tumor imaging probes.
High-resolution whole-body blood vessel imaging of living mice was accomplished, and near-infrared imaging was also used to examine the biodistribution of
QDs. The wide excitation range, resistance to photobleaching, and lack of toxic
heavy metal components that PEGylated Silver Sulphide QDs display are all crucial
for bioimaging. In addition to these fundamental qualities, surface features were
essential for invivo applications since they may directly affect the blood ow and
biodistribution of the NPs. PEG grafting is one of the most popular methods for
extending nanoparticle circulation and enhancing tumor accumulation by lowering
nonspecic binding to proteins and cells. As a result, PEGylated Ag2S QDs offer a
uniform structure for invivo imaging using quantum dots (Lu etal. 2020).
12.2.4 PEGylated Gold NPs forImaging Applications
PEGylated Gold nanoparticles (PEG-AuNPs) are highly biocompatible and have a
variety of potential biological applications. PEG-AuNPs, which have had their surface modied with PEG, can be used to conjugate them with a variety of biological
molecules. Unique features of gold nanoparticles include their small size, excellent
biocompatibility, low toxicity, basic surface chemistry, and ease of surface modication. PEG-AuNPs are up-and-coming prospects for biomedical use with a wide
range of biological applications, including as biosensors and drug delivery vectors
for chemotherapy and radiation therapy for cancer.
However, due to absorption and rapid clearance by the RES, specically macrophages, administration of nanoparticles to target tumor locations is typically constrained. To prevent the absorption of opsonin proteins, PEG-coated NPs
(PEGylation) can provide a hydrophilic protective layer consequently reducing