pH-Dependent Transmembrane Activity of Peptide-Functionalized Gold Nanostars for Computed Tomography/Photoacoustic Imaging and Photothermal Therapy

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• 作者：Ying Tian ; Yunlei Zhang ; Zhaogang Teng ; Wei Tian ; Song Luo ; Xiang Kong ; Xiaodan Su ; Yuxia Tang ; Shouju Wang ; Guangming Lu
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2017
• 出版时间：January 25, 2017
• 年：2017
• 卷：9
• 期：3
• 页码：2114-2122
• 全文大小：673K
• ISSN：1944-8252

文摘

Progress in multifunctional nanomaterials for tumor therapy mostly depends on the development of tumor-targeting delivery strategies. One approach is to explore a pH-responsive strategy to target the slightly acidic solid tumor microenvironment. A novel class of pH (low) insertion peptides (pHLIPs) with pH-dependent transmembrane activity can fold and rapidly insert into the lipid bilayer of tumor cells triggered by acidity, facilitating the cellular internalization of nanomaterials synchronously. Here, we innovatively decorated gold nanostars (GNSs) with pHLIPs (GNS-pHLIP) to improve their targeting ability and photothermal therapeutic (PTT) efficiency. The obtained GNS-pHLIP exhibited the excellent characteristics of uniform size and good biocompatibility. As compared to GNS-mPEG, the cellular internalization of GNS-pHLIP was 1-fold higher after a 2 h incubation with cells in media at pH 6.4 than at pH 7.4. Moreover, the tumor accumulation of the GNS-pHLIP was 3-fold higher than that of GNS-mPEG after intravenous injection into MCF-7 breast tumor animal models for 24 h. Furthermore, GNS-pHLIP exhibited stronger signals than the GNS-mPEG through computed tomography (CT) and photoacoustic (PA) imaging. Simultaneously, the desirable targeting efficiency significantly improved the PTT efficacy to tumors, with low side effects on normal tissues. The results clearly demonstrate that the GNS-pHLIP successfully took advantage of the tumor-targeting ability of pHLIPs and the good characteristics of GNSs, which may contribute to the study of tumor imaging and therapy.