International Journal of Nanomedicine 2011:6
particles, while creatinine decreased with the 60 nm particles,
indicating that the 10 and 60 nm particles caused liver and
kidney damage. The present work clearly shows that 10 and
60 nm PEG-coated gold nanoparticles are not sufﬁciently
safe, and that the 5 and 30 nm particles have relatively low
toxicity. These conclusions are very important for future
cancer therapy, drug delivery, and diagnosis.
The authors would like to thank Professor Warren Chan for
his helpful discussions. This work was supported by the
National Natural Science Foundation of China (Grant No.
81000668, 30970867), the Specialized Research Fund for
the Doctoral Program (SRFDP) of Higher Education State
Education Ministry (Grant No. 200800231058), and the
Subject Development Foundation of Institute of Radiation
Medicine, Chinese Academy of Medical Sciences CAMS.
The authors report no conﬂicts of interest in this work.
1. Daniel MC, Astruc D. Gold nanoparticles: assembly, supramolecular
chemistry, quantum-size-related properties, and applications toward
biology, catalysis, and nanotechnology. Chem Rev. 2004;104:
2. Eustis S, El-Sayed MA. Why gold nanoparticles are more precious than
pretty gold: noble metal surface plasmon resonance and its enhancement
of the radiative and nonradiative properties of nanocrystals of different
shapes. Chem Soc Rev. 2006;35:209–217.
3. Hu M, Chen J, Li ZY, et al. Gold nanostructures: engineering their
plasmonic properties for biomedical applications. Chem Soc Rev.
4. Anker JN, Hall WP, Lyandres O, Shah NC, Zhao J, Van Duyne RP.
Biosensing with plasmonic nanosensors. Nat Mater. 2008;7:442–453.
5. Sokolov K, Follen M, Aaron J, et al. Real-time vital optical imaging
of precancer using anti-epidermal growth factor receptor antibodies
conjugated to gold nanoparticles. Cancer Res. 2003;63:1999–2004.
6. Link S, El-Sayed MA. Shape and size dependence of radiative, non-
radiative and photothermal properties of gold nanocrystals. Int Rev
Phys Chem. 2000;19:409–453.
7. Wu D, Zhang XD, Liu PX, Zhang LA, Fan FY, Guo ML. Gold nano-
structure: fabrication, surface modiﬁcation, targeting imaging, and
enhanced radiotherapy. Curr Nanosci. 2011;7:110–118.
8. Zheng J, Zhang C, Dickson RM. Highly ﬂuorescent, water-soluble,
size-tunable gold quantum dots. Phys Rev Lett. 2004;93:077402.
9. Huang X, El-Sayed IH, Qian W, El-Sayed MA. Cancer cell imaging
and photothermal therapy in the near-infrared region by using gold
nanorods. J Am Chem Soc. 2006;128:2115–2120.
10. Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to
enhance radiotherapy in mice. Phys Med Biol. 2004;49:N309–N315.
11. Juzenas P, Chen W, Sun YP, et al. Quantum dots and nanoparticles for
photodynamic and radiation therapies of cancer. Adv Drug Deliv Rev.
12. Liu CJ, Wang CH, Chien CC, et al. Enhanced x-ray irradiation-induced
cancer cell damage by gold nanoparticles treated by a new synthesis
method of polyethylene glycol modification. Nanotech. 2008;19:
13. Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the
nanolevel. Science. 2006;311:662–627.
14. Chen Z, Meng H, Xing G, et al. Acute toxicological effects of copper
nanoparticles in vivo. Toxicol Lett. 2006;163:109–120.
15. Cho EC, Au L, Zhang Q, Xia Y. The effects of size, shape, and surface
functional group of gold nanostructures on their adsorption and
internalization by cells. Small. 2009;6:517–522.
16. Sayes CM, Reed KL, Warheit DB. Assessing toxicity of ﬁne and
nanoparticles: comparing in vitro measurements to in vivo pulmonary
toxicity proﬁles. Toxicol Sci. 2007;97:163–180.
17. Kim JS, Yoon TJ, Yu KN, et al. Toxicity and tissue distribution of
magnetic nanoparticles in mice. Toxicol Sci. 2006;89:338–347.
18. Yang ST, Fernando KAS, Liu JH, et al. Covalently PEGylated carbon
nanotubes with stealth character in vivo. Small. 2008;4:940–944.
19. Goodman CM, McCusker CD, Yilmaz T, Rotello VM. Toxicity of
gold nanoparticles functionalized with cationic and anionic side chains.
Bioconjug Chem. 2004;15:897–900.
20. Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD. Gold nano-
particles are taken up by human cells but do not cause acute cytotoxicity.
21. Pernodet N, Fang X, Sun Y, et al. Adverse effects of citrate/gold nano-
particles on human dermal ﬁbroblasts. Small. 2006;2:766–773.
22. Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small.
23. Murphy CJ, Gole AM, Stone JW, et al. Gold nanoparticles in
biology: beyond toxicity to cellular imaging. Acc Chem Res. 2008;41:
24. Teeguarden JG, Hinderliter PM, Orr G, Thrall BD, Pounds JG.
Particokinetics in vitro: dosimetry considerations for in vitro
nanoparticle toxicity assessments. Toxicol Sci. 2007;95:300–312.
25. Patra HK, Banerjee S, Chaudhuri U, Lahiri P, Dasgupta A. Cell selective
response to gold nanoparticles. Nanomedicine. 2007;3:111–119.
26. Male KB, Lachance B, Hrapovic S, Sunahara G, Luong JH. Assessment
of cytotoxicity of quantum dots and gold nanoparticles using cell-based
impedance spectroscopy. Anal Chem. 2008;80:5487–5493.
27. Chithrani BD, Ghazani AA, Chan WCW. Determining the size and
shape dependence of gold nanoparticle uptake into mammalian cells.
Nano Lett. 2006;6:662–668.
28. Pan Y, Neuss S, Leifert A, et al. Size-dependent cytotoxicity of gold
nanoparticles. Small. 2007;3:1941–1949.
29. Manna S, Sarkar S, Barr J, Wise K, et al. Single-walled carbon nanotube
induces oxidative stress and activates nuclear transcription. Nano Lett.
30. Schipper M, Nakayama-Ratchford N, Davis C, et al. A pilot toxicology
study of single-walled carbon nanotubes in a small sample of mice. Nat
31. Sayes CM, Marchione AA, Reed KL, Warheit DB. Comparative
pulmonary toxicity assessments of C
water suspensions in rats: few
differences in fullerene toxicity in vivo in contrast to in vitro proﬁles.
Nano Lett. 2007;7:2399–2406.
32. De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJ, Geertsma RE.
Particle size-dependent organ distribution of gold nanoparticles after
intravenous administration. Biomaterials. 2008;29:1912–1919.
33. Sonavane G, Tomoda K, Makino K. Biodistribution of colloidal gold
nanoparticles after intravenous administration: effect of particle size.
Colloids Surf B Biointerfaces. 2008;66:274–280.
34. Kim JH, Kim JH, Kim KW, Kim MH, Yu YS. Intravenously
administered gold nanoparticles pass through the blood-retinal
barrier depending on the particle size, and induce no retinal toxicity.
35. Chen YS, Hung YC, Liau I, Huang GS. Assessment of the in vivo
toxicity of gold nanoparticles. Nanoscale Res Lett. 2009;4:858–864.
36. Cho WS, Kim S, Han BS, Son WC, Jeong J. Comparison of gene
expression proﬁles in mice liver following intravenous injection of 4 and
100 nm-sized PEG-coated gold nanoparticles. Toxicol Lett. 2009;191:
submit your manuscript | www.dovepress.com
Zhang et al