Gold Nanoparticles Stabilized with MPEG-Grafted Poly(l-lysine): in Vitro and in Vivo Evaluation of a Potential Theranostic Agent

详细信息    查看全文

• 作者：Alexei A. Bogdanov ; Jr. ; Suresh Gupta ; Nadezhda Koshkina ; Stuart J. Corr ; Surong Zhang ; Steven A. Curley ; Gang Han
• 刊名：Bioconjugate Chemistry
• 出版年：2015
• 出版时间：January 21, 2015
• 年：2015
• 卷：26
• 期：1
• 页码：39-50
• 全文大小：581K
• ISSN：1520-4812

文摘

As the number of diagnostic and therapeutic applications utilizing gold nanoparticles (AuNPs) increases, so does the need for AuNPs that are stable in vivo, biocompatible, and suitable for bioconjugation. We investigated a strategy for AuNP stabilization that uses methoxypolyethylene glycol-graft-poly(l-lysine) copolymer (MPEG-gPLL) bearing free amino groups as a stabilizing molecule. MPEG-gPLL injected into water solutions of HAuCl₄ with or without trisodium citrate resulted in spherical (Z_av = 36 nm), monodisperse (PDI = 0.27), weakly positively charged nanoparticles (AuNP3) with electron-dense cores (diameter: 10.4 卤 2.5 nm) and surface amino groups that were amenable to covalent modification. The AuNP3 were stable against aggregation in the presence of phosphate and serum proteins and remained dispersed after their uptake into endosomes. MPEG-gPLL-stabilized AuNP3 exhibited high uptake and very low toxicity in human endothelial cells, but showed a high dose-dependent toxicity in epithelioid cancer cells. Highly stable radioactive labeling of AuNP3 with ^99mTc allowed imaging of AuNP3 biodistribution and revealed dose-dependent long circulation in the blood. The minor fraction of AuGNP3 was found in major organs and at sites of experimentally induced inflammation. Gold analysis showed evidence of a partial degradation of the MPEG-gPLL layer in AuNP3 particles accumulated in major organs. Radiofrequency-mediated heating of AuNP3 solutions showed that AuNP3 exhibited heating behavior consistent with 10 nm core nanoparticles. We conclude that PEG-pPLL coating of AuNPs confers 鈥渟tealth鈥?properties that enable these particles to exist in vivo in a nonaggregating, biocompatible state making them suitable for potential use in biomedical applications such as noninvasive radiofrequency cancer therapy.