Role of Antibody-Mediated Tumor Targeting and Route of Administration in Nanoparticle Tumor Accumulation in Vivo

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• 作者：Niladri Chattopadhyay ; Humphrey Fonge ; Zhongli Cai ; Deborah Scollard ; Eli Lechtman ; Susan J. Done ; Jean-Philippe Pignol ; Raymond M. Reilly
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：August 6, 2012
• 年：2012
• 卷：9
• 期：8
• 页码：2168-2179
• 全文大小：793K
• 年卷期：v.9,no.8(August 6, 2012)
• ISSN：1543-8392

文摘

In this study, we have looked at enhancing tumor uptake and intracellular delivery of gold nanoparticles (AuNPs) while reducing the systemic exposure by systematic evaluation of the impact of targeting and route of administration on organ distribution. High-resolution microSPECT/CT imaging was used to track the in vivo fate of ¹¹¹In-labeled nontargeted and human epidermal growth factor receptor-2 (HER-2) targeted AuNPs following intravenous (i.v.) or intratumoral (i.t.) injection. For i.v. injection, the effects of GdCl₃ (for deactivation of macrophages) and nonspecific (anti-CD20) antibody rituximab (for blocking of Fc mediated liver and spleen uptake) were studied. It was found that HER-2 targeting via attachment of trastuzumab paradoxically decreased tumor uptake as a result of faster elimination of the targeted AuNPs from the blood while improving internalization in HER-2-positive tumor cells as compared to nontargeted AuNPs. I.T. injections with HER-2 targeted AuNPs resulted in high tumor retention with low systemic exposure and represents an attractive delivery strategy. Our results provide a strategy for optimizing tumor delivery and quantifying organ distribution of this widely studied class of nanomaterial.

Keywords:

HER2; nanoparticles; microSPECT; intratumoral; imaging; ICP-MS; biodistribution; lymph node; pharmacokinetics; antibody