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Gold Nanoparticles:A Boon to Drug Delivery System

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DOI: 10.22205/sijbs/2015/v1/i3/100407

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South Indian Journal of Biological Sciences 2015; 1(3); 127-133 Online ISSN:2454-4787

Gold nanoparticles: a boon to drug delivery system

Kashif Hussain1, Touseef Hussain 2,*
Gyani Inder Singh Institute of Professional Studies, Dehradun, Dehradun, Uttarakhand 248003, India
1

Deptartment of Life Science, Uttarakh and Technical University, Dehradun, Uttarakhand 248003, India
2

*Corresponding authors:
Touseef Hussain
E-mail: hussaintouseef@yahoo.co.in

Manuscript details Abstract

Article History: Gold nanoparticles (AuNPs) are currently playing a significant role for human
Received 9 October 2015 welfare in the field of clinical diagnosis as well as several biomedical applications.
Revised 22 November 2015 More and more research shows that AuNPs-based technologies are becoming
Accepted 8 December 2015 promising approaches in diabetes, cancer research, chemotherapy, AIDS treat-
Published 28 December 2015 mentetc.AuNPs can be easily synthesized, functionalized, and are biocompatible.
The tenability of theAuNP monolayer allows for complete control of surface prop-
erties for targeting and stability/release using these nanocarriers.Nanoplatforms
Keywords: have been developed to manufacture of nanomedicines in preclinical and clinical
Gold nanoparticles studies for the administration of small molecules, genes, and peptides with im-
AuNPs provement of given in vivo behaviour. Similarly, NPs emerge as the future of drug
Nano carriers delivery technology as they might be future crucial diagnostic and therapeutic
Gene delivery tools. Of these, gold nanoparticles with their unique chemical and physical prop-
erties have emerge as promising carrier for delivery of various molecules with
therapeutic properties.This review will discuss several delivery strategies utilizing
AuNPs.

1. Introduction cells, stability over high temperatures and transloca-

Nanotechnology has provided research-level break-
through in various industrial applications. Among
those it has attained remarkable levels in medicine
(bio diagnostics, drug delivery and cancer therapy)
(Ferrari 2005; Rosi and Markin 2005). These achieve-
ments came from the usage of versatile nanomateri-
als.Nanomaterials are materials with the sizes in the
range of 1 to several 100’s of nanometers, attracts an
ample attention in different fields of physics, chem-
istry, material science, medicine and biology, due to
their unique electronic, magnetic, optical, mechan-
ical, physical and chemical properties. The char-
acteristic properties of nanoparticles are their (a)
small size (1–100 nm), (b) large surface-to-volume
ratio, (c) physical and chemical properties that can
be tuned depending upon the requirements of size,
composition, and shape, (d) quantitative and qualita-
tive target-binding properties and (e) high robustness
shown by some of the nanostructure materials (Gu-
nasekera et al., 2009). In recent years, the use of metal
nanoparticles has expanded in biomedical research.
They are used in diagnosis and therapeutics due to
their unique properties of high reactivity to the living
tion into the cells, etc.. They also exhibit exceptional
optical properties making them capable of producing
quantum effects suitable for imaging applications.
Most commonly studied metal nanoparticles include
gold, silver, titanium oxide and iron nanoparticles
(El-Ansary and Al-Daihan 2009).
2. Drug delivery
Drug delivery is the method or process of adminis-
tering a pharmaceutical compound to achieve a ther-
apeutic effect in humans or animals. Drug delivery
technologies are patent protected formulation tech-
nologies that modify drug release profile, absorption,
distributionand elimination for the benefit of improv-
ing product efficacyand safety, as well as patient con-
venience and compliance. Current efforts in the area
of drug delivery include the development of targeted
delivery in which the drug is only active in the target
area of the body (for example, in cancerous tissues or
other diseased tissues) and sustained release formu-
lations in which the drug is released over a period of
time in a controlled manner from a formulation.At
present, there are 30 main drug delivery products on-
the market. The total annual income for all of these is

128
approximately US$33 billion with an annual growth
of 15 % (based on global product revenue). The rea-
sons for this increasing interest in drug delivery are
due to the increasing need of safe drugs, capable of
reaching the target and with minimal side effects.
In fact the main problems associated with system-
ic drug administration are essentially related to the
bio-distribution of pharmaceuticals throughout the
body. This indiscriminate distribution means that,
to achieve a required therapeutic concentration the
drug has to be administered in large quantities, the
major part of which is just wasted in normal tissues.
Ideally, a ‘‘perfect’’ drug should exert its pharmaco-
logical activity only at the target site, using the lowest
concentration possible and without negative effects
on non-target compartments (Pierige et al., 2005).
The process for delivering a drug is as important
as the actual activity of the drug in determining the
therapeutic effect. For optimum therapeutic effect,
the right amount of a drug needs to get to the right
place at the right time. Consequently, advanced drug
delivery formulations have been developed over the
past 20 years that do not simply release a drug at a
specific rate, but release the drug in a way that the
pharmaceutical scientists and engineers have de-
signed. Additionally, because drug delivery can im-
prove safety, efficacy, convenience and patient com-
pliance, improving delivery methods has become a
major focus of pharmaceutical companies. In tradi-
tional drug delivery, common delivery routes include
oral, pulmonary, transdermal and injection, and they
each have certain advantages and disadvantages as-
sociated with them. For instance, all of these routes,
except for direct injection into a vein or muscle tis-
sue, have cellular layers that are encountered, which
function as a barrier to transport into the systemic
circulation. Controlled release in drug delivery can
Fig.1. Schematic illustration of potential applications of
gold nanoparticles in biology and medicine.
significantly enhance the therapeutic effect of a drug.
Typically, controlled release is used to achieve sus-
129
tained or pulsatile drug release. Sustained release is
used to achieve a constant release of a drug over an
extended period of time. For example, many drugs
have an optimum range of concentrations that if
the concentration of the drug is above or below this
range, the drug is toxic or has no therapeutic effect,
respectively (Fig.1).
Development of nonocarriers is a novel area of
science thatprovides, with a new hope, the tools and
technology to work at atomic, molecular and supra-
molecular levels leading to creation of devices and
delivery systems with fundamentally new proper-
ties and functions. These carriers offer a number of
advantages making it an ideal drug delivery vehi-
cle.Drug release and transport are major factors for
Fig.2. Schematic diagram of theranostic gold nanoparticle.
creating an efficient DDS (Drug Delivery System).
Nano-carriers can be loaded with drugs through
non-covalent interactions or by covalent conjuga-
tion.Gold nanoparticles are suitable for the delivery
of the drugs to cellular destinations due to their ease
of synthesis, functionalization and biocompatibili-
ty. Gold nanoparticles functionalized with targeted
specific biomolecules can effectively destroy cancer
cells or bacteria (Fig. 2) (Duncan et al., 2010). Large
surface to volume ratio of gold nanoparticles offer a
large number of drug molecules being carried by the
gold nanoparticles (Grace and Pandian 2007). Gold
nanoparticles have been used for the co-adminis-
tration of protein drugs due to their ability to cross
cellular membranes, possibly due to the interaction
of gold nanoparticles with cell surface lipids.Surface
modification of gold nanoparticles would present
four major benefits, (i) it could increase the circula-
tion lifetime of conjugates by preventing or slowing
their removal by Reticulo-Endothelial System (RES),
(ii) drug molecules could specifically located and at-
tach to targeted cells, (iii) the stability could be im-
proved and (iv) the non-specific cytotoxicity could be
reduced by capping gold nanoparticles (Fig.3).
One of the greatest challenges facing chemothera-
py today is developing drug delivery systems (DDSs)
that are efficacious and have therapeutic selectivity.
Both passive and active targeting approaches have

Fig.3. Functionalized GNP’s (fGNP’s) for drug delivery.
been utilized with nanocarriers such as dendrimers,
liposomes, metal nanoparticles, polymer micelles and
vesicles. These DDSs have improved in the targeted
delivery of the therapeutics for cancer treatment. The
application of gold nanoparticles (AuNPs) as a DDS is
a rapidly expanding field (Gibson et al., 2007; Paciotti
et al., 2006). Their inherent properties make them a
very promising vehicle for drug delivery. Controlled-
fabrication of various sized particles (1–150 nm) with
limited size dispersity has been established (Schmid
1992) and using ligand place exchange reactions
(Templeton et al., 1999), multifunctionalmonolayers
can be fabricated. This structural diversity enables
particle surfaces to containmultiple targeting agents
and/or chemotherapeutics.
The gold nanoparticles can also be used in an ul-
trasensitive assay technique to detect cancers (Shipp
2006). Peng et al. (2009) introduced the functional-
ized gold nanoparticles in combination with the pat-
tern recognition methods to diagnose the lung cancer
from breath testing. This method is an in vitro sensor
array technique of the detection of biomarkers in ex-
haled breath of lung cancer patients asa non-invasive
diagnostic tool. In addition, Thaxton et al. (2009)
reported the combination system based on the mag-
netic microparticles and the gold nanoparticles con-
jugated with the prostate-specific antigen- (PSA-)
specific antibodies to diagnose prostate cancers. In
this system, the magneticmicroparticles conjugated
with PSA-specific antibodies were used to extract the
traceable amounts of PSA in the serum samples from
patients, and the gold nanoparticles with PSAspecifi-
cantibodies and short DNA sequences (the barcodes)
were attached to detect this analyte for in vitro bar-
code assay.
3. Role of Gold nanoparticles in nanobiotechnology
Gold (Au) is unique compared to other metals be-
cause of its resistance to tarnishing. According to
the earliest records, use of Au for medical purposes
can be traced back to the Chinese civilization in 2500
BC, and after that, several ancient cultures have uti-
lized Au-based materials for medicinal purpose for
the treatment of a variety of diseases such as small-
pox, skin ulcers, measles, and syphilis. In today’s era
of nanotechnology, gold nanoparticles (AuNPs) have
been used for the treatment of diseases like rheuma-
130
toid arthritis, and so forth, while considerable re-
search is currently going on for unveiling potential
anticancer and antimicrobial and biodiagnostic ap-
plications of Au-based materials and compounds for
clinical applications.
In the recent years, nanotechnology has attracted
most of the scientific community concerning the ap-
plications of nanotechnology in medicine. One par-
ticularly exciting field of research involves the use of
AuNPs for the diagnosis of cancer. AuNPs find signif-
icant exploitations in biomedical field due to:
➢ Their comparative chemical stability, making them
less hazardous,
➢ Simple and straightforward synthesis and fabrica-
tion process, and
➢ Genuine biocompatibility and non-interference
with other labelled biomaterials (e.g. antibody and
other biomarkers).
Furthermore, the advancement of nanotechnology
has led researchers to generate nanostructures that
can be conjugated to several kinds of biological mole-
cules, including hormones and antibodies, which can
reach targeted cells expressing the receptors. Colloi-
dal Au has been playing an important role for cur-
ing various diseasesalthough the exact mechanism of
action is still poorly understood. Today, the applica-
tions of AuNPs are increasing day by day in pharma-
ceutical sciences for human welfare. It can be used
to understand more about the nature of diseases like
cancer and HIV by providing significant target with
nano-vehicles.
3.1 The advantages of using nanoparticles as a drug
delivery system include the following
➢ Particle size and surface characteristics of nanopar-
ticles can be easily manipulated to achieve both pas-
sive and active drug targeting after parenteral admin-
istration.
➢ They control and sustain release of the drug during
the transportation and at the site of localization, al-
tering organ distribution of the drug and subsequent
clearance of the drug so as to achieve increase in drug
therapeutic efficacy and reduction in side effects.
➢ Drug loading is relatively high and drugs can be
incorporated into the systems without any chemical
reaction.
➢ Site-specific targeting can be achieved by attaching
targeting ligands to surface of particles or use of mag-
netic guidance.
➢ The system can be used for various routes of ad-
ministration including oral, nasal, parenteral, in-
tra-ocular etc.
➢ Avoidance of coalescence leads to enhanced phys-
ical stability.
➢ Reduced mobility of incorporated drug molecules
leads to reduction of drug leakage.
➢ Static interface solid/liquid facilitates surface mod-
ification.
3.2 Disadvantages of nanoparticles
3.2.1. Potential toxicity
While the small size of nanoparticle is what makes
them so useful in medicine, it is also the factor that
might make them potentially dangerous to human
health.
3.2.2. Environmental concerns
Artificially manufacture nanoparticles will be new to
the environment in type and quantity and would con-
stitute a new class of non biodegradable pollutants.
4. Ideal properties of nanoparticles
➢ Natural or synthetic polymer
➢ Inexpensive
➢ Nontoxic
➢ Biodegradable
➢ Nonthrombogenic
➢ Nonimmunogenic
➢ Particle diameter <100nm
➢ No platelet aggregation
➢ Noninflammatory
➢ Prolonged circulation time
4.1 Applications of targeted delivery systems from
cells to clinics
Nano platforms generally have the potential to be
applied as cancer diagnosis, imaging, and treatment
in vitro and in vivo. Targeted delivery strategies of
nano platforms are special formulations and carriers
with anticancer drugs such as pegylated liposomes,
polymeric nanoparticles/micelles, and albumin-
based drug carriers. These nanoplatforms that we
mentioned above can be applicable to the biomedical
approaches such as cancer diagnostics (Kateb et al.,
2011), anticancer therapy (Muthu and Wilson 2010),
nano-imaging (Bulte and Modo 2007), bimodal
imaging (Jarzyna et al., 2010; Janczewski et al., 2011),
and real-time intra-operative imaging (Van Dam et
al., 2011). The FDA has approved clinical use of a
significant number of anticancer drug products in
the nanometer size range including the applications.
In particular, nanoimaging has become based on the
diagnostic potential of an earlier detection in the
cancer and other human diseases (Jarzyna et al., 2010).
In the case of bimodal contrast imaging, bimodal
contrast agents allow the assessment of regions of
interest using two independent imaging modalities
such as MRI reagents and fluorescent agents. In the
case ofMRI and fluorescence imaging, MRI has an
excellent spatial resolution, and fluorescence imaging
compensates for the sensitivity of MRI overcoming
the limitations of a single-modality imaging (Jeff
and Bulte 2008). For intra-operative fluorescence
imaging, the first human trial in advanced-stage
131
ovarian cancer proceeded with tumorsSpecific folate
receptor-αtargeted fluorescent agent (Van Dam 2011).
This study offers the potential application of intra-
operative staging with tumor-specific fluorescence
imaging in patients with ovarian cancer by folate
receptor-αoverexpression.
Gold nanoparticles based on gold cores are an-
otherversatile platform that provides desirable val-
uesfortheranostic systems (Chan et al., 2013). They
are preparedwith core size from 1.5 to 10 nm, pro-
viding large areafor efficient drug and ligand conju-
gations (Link and Al-Sayed 2002). Goldnanoparticles
are commonly synthesized by chemicaltreatment of
hydrogen tetrachloroaurate. The therapeutic load-
ing are achieved by eithernon covalent interaction
(e.g. via electrostatic interaction)or covalent chem-
ical conjugation of (i.e., organic drug).The inherent
features of gold nanoparticles include diagnostic
property, tunable core size, mono dispersity, low tox-
icity, large surface to volume ratio, surface plasmon
absorption, ability to bind to biomoleculesvia Au–S
bonds, light-scattering propertiesand ease of fabri-
cation (Connor 2005; Kumar et al., 2013). Recently,
gold nanoparticlesshowed the possibility of treating
MDR tumors by targeted photothermal treatment in
combinationwith a chemotherapeutic agent (Lee et
al., 2014). Heo etal. (2012) described gold nanopar-
ticles surface-functionalized with PEG, biotin, pa-
clitaxel and rhodamine B linked beta-cyclodextrin
(beta-CD) as theranostic platform. Paclitaxel formed
inclusioncomplex with beta-CD which was then
conjugatedwith gold nanoparticles. In vitro studies
suggest that gold nanoparticles have higher affinity
towards cancercells such as HeLa, A549 and MG63
in comparisonto NIH3T3 cells. Furthermore, gold
nanoparticles displayed significant cytotoxic effect
against HeLacancer cells.
In another work, smart theranostic gold nanopar-
ticles were developed i.e., DOX was conjugat-
ed togold nanoparticles via Au-S bond by using a
peptide substrate, Cys-Pro-Leu-Gly-Leu-Ala-Gly-
Gly(CPLGLAGG), which is specifically cleaved by the
protease (Fig. 4). The animal studies showed thatafter
injection of the functionalized gold nanoparticlesto
the tumor-bearing mice, the over-expressed protease
Fig.4. Schematic presentation of site specific drug delivery
usingnanocarrier systems
in tumor tissue and intracellular glutathione haveled
to the rapid release of DOX from the functionalized-
gold nanoparticles. Here, enhanced efficacy on tumor
growth inhibition and fluorescent imaging wasreal-
ized simultaneously. The gold nanoparticles with-
stimulus responsive drug release property showed a
promising smart theranostic application for concur-
rentcancer diagnosis and therapy (Chen et al., 2013).
5. Drug delivery strategies using gold nanoparticle
platforms
Drug release and transport are major factors for cre-
ating an efficient DDS. Nano carriers can be loaded
with drugs through non-covalent interactions or by
covalent conjugation (Torchilin 2001) using a pro-
drug that is processed by the cell (Morgan et al.,
2006). AuNPs provide an excellent platform for DDS
design due to the functional versatility of their mono-
layers.
6. Photo-regulated release
Regulation of drug release is crucial for DDSs. One
useful approach for controlling therate and site of re-
lease is to use an external stimulus to trigger release
(Kim et al., 2006). Photo cleavable “cages” have been
used to reduce the activity of a drug, with activation
occurring upon un-caging (MaCoy et al., 2007). Na-
kanishi et al. (2009) have used this approach to de-
velop a photo responsive nano carrier of amines. Us-
ing near-UV irradiation, a carbamate linkage could
be dissociated by the photo cleavable reaction of the
2-nitrobenzyl group. They foundhistamine had no
biological activity while caged but after irradiation
it became active. In further studies the authors ob-
served light-controlled release of the anticancer drug
5-fluorouracil from AuNPs (Agasti et al., 2009). The
mixed monolayer of the AuNPs was composed of
photo cleavable moieties and zwitterionic ligands.
Improved solubility and limited cellular uptake was
achieved by the useof the zwitterionic ligand. Using
near-UV irradiation (365 nm) the photo cleavable
orthonitrobenzyl group could efficiently cleave the
5-fluorouracil from the AuNP. Theobserved IC50 val-
ue on a per particle basis for the AuNP was 0.7 μM.
No significant celldeath was observed in cells treated
with only light AuNPs or only light.
7. Design of lipid-based drug delivery system
Several LBDDS have been developed over the years,
most of them for oral delivery. Hauss (2007), has giv-
en a comprehensive summary of the development,
characterization and use of oral lipid based formula-
tions from both physicochemical and biopharmaceu-
tical perspectives. Approaches in the design can be
separated in 2 categories: lipid-based formulations,
and lipid carriers as particulate systems (liposomes,
solid lipid nanoparticles, lipid implants, lipid micro-
tubules and micro cylinders, lipid micro bubbles, li-
pospheres, microspheres, pellets, nanostructure lipid
carrier) (Chakraborty, 2009).
8. Conclusion
AuNPs show great potential for the creation of DDSs.
132
Their stability, tunable monolayers, functional flexi-
bility, low toxicity, and ability to control the release
of drugs offer manypossibilities for further devel-
opment of DDSs. Additional investigations of these
systemswill be required to fully understand their
pharmacokinetics, interactions with the immunesys-
tem, and the extent of cytotoxicity due to surface and
size of the AuNPs. Continuedresearch into these na-
noscale delivery vehicles will expand the understand-
ing of theinteractions of these materials with biologi-
cal systems, and promoting the development ofmore
effective DDSs.
Conflict of interest statement
We declare that we have no conflict of interest.
References
1. Agasti SS, Chompoosor A, You CC, Ghosh P, Kim CK, Rotel-
lo VM. (2009). Photoregulated release of caged anticancer drugs
from gold nanoparticles. Journal of the American Chemical Soci-
ety, 131(16), 5728–5729.
2. Bulte JW, Modo M. (2007). Nanoparticles in Biomedical Imag-
ing: Emerging Technologies and Applications. Springer, NewYork,
NY, USA.
3. Chakraborty S. (2009). Lipid - an emerging platform for oral
delivery of drugs with poor bioavailability. European Journal of
Pharmaceutics and Biopharmaceutics,73(1), 1-15.
4. Chen H, Zhang X, Dai S. (2013).Multifunctional gold nano star
conjugates for tumor imaging and combined photothermal and
chemo-therapy. Theranostics, 3(9),633-49.
5. Chen WH, Xu XD, Jia HZ. (2013). Therapeutic nanomedicine
based on dual-intelligent functionalized gold nanoparticles for
cancer imaging and therapyin vivo. Biomaterials. 34(34), 8798-
8807.
6. Connor EE, Mwamuka J, Gole A. (2005). Gold nanoparticles
are taken up by human cells but do not cause acute cytotoxicity.
Small, 1(3), 325-327.
7. Duncan B, Kim C, Rotello VM. (2010). Gold nanoparticle plat-
forms as drug and biomacromolecule delivery systems. Journal of
Controlled Release, 148, 122–127.
8. El-Ansary A, Al-Daihan S. (2009). On the toxicity of thera-
peutically used nanoparticles: An overview. Journal of Toxicology,
754810.
9. Ferrari M. (2005). Cancer nanotechnology: opportunities and
challenges, Nat. Rev Cancer,5, 161–171.
10. Gibson JD, Khanal BP, Zubarev ER. (2007). Paclitaxel-func-
tionalized gold nanoparticles. Journal of American Chemical Soci-
ety, 129(37),11653–11661.
11. Grace NA, Pandian K. (2007). Antibacterial efficacy of amino-
glycosidic antibiotics protected gold nanoparticles-A brief study.
Colloids Surface A, 297, 63–70.
12. Gunasekera UA, Pankhurst QA, Douek M. (2009). Imaging
applications of nanotechnology in cancer. Targeted Oncology, 4,
169–181.
13. Hauss DJ. (2007). Oral lipid-based formulations. Advanced
Drug Delivery Reviews, 59(7), 667-76.
14. Heo DN, Yang DH, Moon HJ. (2012). Gold nanoparticles
surface-functionalized with paclitaxel drug and biotin receptor
as theranostic agents for cancer therapy. Biomaterials, 33(3), 856-
866.
15. Janczewski D, Zhang Y, Das GK. (2011). Bimodal magnetic
fluorescent probes for bioimaging. Microscopy Research and Tech-
nique, 74(7), 563–576.
 16. Jarzyna PA, Gianella A, Skajaa T. (2010). Multifunctional im-
aging nanoprobes. Wiley Interdisciplinary Reviews, 2(2),138–150.
17. Jeff MMJM, Bulte WM. (2008). Nanoparticles in biomedical
imaging, emerging technologies and applications. Fundamental
Biomedical Technologies, Springer, New York, NY, USA, 102.
18. Kateb B, Chiu K, Black KL. (2011). Nanoplatforms for con-
structing new approaches to cancer treatment, imaging, and drug
delivery:What should be the policy?. Neuro Image, 54(1), S106–
S124.
19. Kim HJ, Matsuda H, Zhou H, Honma I. (2006). Ultra-
sound-triggered smart drug release from a poly(dimethylsilox-
ane)- mesoporous silica composite. Advanced Materials, 18(23),
3083–3088.
20. Kumar R, Korideck H, Ngwa W. (2013). Third generation gold
nanoplate form optimized for radiation therapy. Translational
Cancer Research, 2(4).
21. Lee SM, Kim HJ, Kim SY. (2014). Drug-loaded gold plasmon-
ic nanoparticles for treatment of multidrug resistance in cancer.
Biomaterials, 35(7), 2272-2282.
22. Link S, El-Sayed MA. (2002). Shape and size dependence
of radiative, non-radiative and photothermal properties of gold
nanocrystals. International Reviews in Physical Chemistry, 19 (3),
409-453.
23. McCoy CP, Rooney C, Edwards CR, Jones DS, Gorman SP.
(2007). Light-triggered molecule-scale drug dosing devices. Jour-
nal of the American Chemical Society, 129(31), 9572–9573.
24. Morgan MT, Nakanishi Y, Kroll DJ, Griset AP, Carnahan
MA, Wathier M, Oberlies NH, Manikumar G, Wani MC, Grin-
staff MW. (2006). Dendrimer-encapsulated camptothecins: in-
creased solubility, cellular uptake, and cellular retention affords
enhanced anticancer activity in vitro. Cancer Research, 66(24),
11913–11921.
25. Muthu MS, Wilson B. (2010). Multifunctional radionano-
medicine: a novel nanoplatform for cancer imaging and therapy.
Nanomedicine, 5(2), 169–171.
26. Nakanishi J, Nakayama H, Shimizu T, Ishida H, Kikuchi Y,
133
View publication stats
Yamaguchi K, Horiike Y. (2009). Light-regulated activation of
cellular signaling by gold nanoparticles that capture and release
amines. Journal of the American Chemical Society, 131(11), 3822–
3823.
27. Paciotti GF, Kingston DGI, Tamarkin L. (2006).Colloidal gold
nanoparticles: a novel nanoparticle platform for developing mul-
tifunctional tumor-targeted drug delivery vectors. Drug Develop-
ment Research, 67(1),47–54.
28. Peng G, Tisch U, Adams O. (2009). Diagnosing lung cancer in
exhaled breath using gold nanoparticles. Nature Nanotechnology,
4(10), 669–673.
29. Pierige F, Serafini S, Rossi L, Magnani M. (2008). Cell-based
drug delivery. Advanced Drug Delivery Reviews, 60, 286–295.
30. Rosi NL, Mirkin CA. (2005). Nanostructures in biodiagnos-
tics. Chemical Reviews,105, 1547–1562.
31. Schmid G. (1992). Large clusters and colloids, metals in the
embryonic state. Chemical Reviews, 92(8), 1709–1727.
32. Shipp G. (2006). Ultrasensitive measurement of protein and
nucleic acid biomarkers for earlier disease detection and more
effective therapies. Biotechnology Healthcare Journal, 3(2), 35– 40.
33. Templeton AC, Wuelfing WP, Murray RW. (1999). Monolay-
er-protected cluster molecules. Accounts of Chemical Research,
33(1), 27–36.
34. Thaxton CS, Elghanian R, Thomas AD. (2009). Nanoparticle
based bio-barcode assay redefines “undetectable” PSA and bio-
chemical recurrence after radical prostatectomy. Proceedings of
the National Academy of Sciences of the United States of America,
106(44), 18437–18442.
35. Torchilin VP. (2001). Structure and design of polymeric sur-
factant-based drug delivery systems. Journal of Controlled Re-
lease, 73(2–3), 137–172.
36. Van Dam GM, Themelis G, Crane LMA. (2011). Intraopera-
tive tumor-specific fluorescence imaging in ovarian cancer by fo-
late receptor- α targeting: first in-human results. Nature Medicine,
17(10), 1315–1319.