Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.
State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, People's Republic of China.
ACS Appl Mater Interfaces. 2017 Jan 25;9(3):2114-2122. doi: 10.1021/acsami.6b13237. Epub 2017 Jan 13.
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.
多功能纳米材料在肿瘤治疗方面的进展主要取决于肿瘤靶向递药策略的发展。一种方法是探索一种 pH 响应策略，以靶向略酸性的实体肿瘤微环境。一类具有 pH 依赖性跨膜活性的新型 pH（低）插入肽（pHLIP）在酸度触发下可以折叠并迅速插入肿瘤细胞的脂质双层中，从而促进纳米材料的细胞内化。在这里，我们创新性地用 pHLIP（GNS-pHLIP）修饰金纳米星（GNS），以提高其靶向能力和光热治疗（PTT）效率。所得的 GNS-pHLIP 表现出均匀尺寸和良好的生物相容性的优异特性。与 GNS-mPEG 相比，在 pH 6.4 的培养基中孵育 2 小时后，GNS-pHLIP 的细胞内化率比在 pH 7.4 时高 1 倍。此外，静脉注射 MCF-7 乳腺癌动物模型 24 小时后，GNS-pHLIP 的肿瘤积累量是 GNS-mPEG 的 3 倍。此外，GNS-pHLIP 通过计算机断层扫描（CT）和光声（PA）成像显示出比 GNS-mPEG 更强的信号。同时，理想的靶向效率显著提高了肿瘤的 PTT 疗效，对正常组织的副作用低。结果清楚地表明，GNS-pHLIP 成功地利用了 pHLIP 的肿瘤靶向能力和 GNS 的良好特性，这可能有助于肿瘤成像和治疗的研究。
