Zhong Yaping, Zou Yibiao, Liu Lingyan, Li Ruohan, Xue Fengfeng, Yi Tao
Department of Chemistry and Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, 2005 Songhu Road, Shanghai 200438, China; Hubei Key Laboratory of Advanced Textile Materials & Application, Institute of Technology, Wuhan Textile University, Wuhan 430200, China.
Department of Chemistry and Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
Acta Biomater. 2020 Oct 1;115:358-370. doi: 10.1016/j.actbio.2020.08.007. Epub 2020 Aug 13.
Heat-treated cancer cells have thermo-resistance due to the up-regulated levels of heat shock proteins (HSP) resulting in low therapeutic efficiency and ineffective ablation of tumors. In this work, we report pH-responsive AgS nanodots (AgS NDs) loaded with HSP70 inhibitor (QE-PEG-AgS) for enhanced photothermal cancer therapy. QE-PEG-AgS was easily prepared via self-assembly of hydrophobic AgS NDs, amphiphilic pH-responsive PEG-PAE polymer, and an HSP70 inhibitor quercetin (QE). QE-PEG-AgS has ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The slightly acidic environment of tumor cells and the acidity of lysosomes as well as the high temperature generated by photothermal therapy under irradiation of NIR light (808 nm) promote the release of the inhibitor molecules to reduce the heat resistance of cancer cells and improve the in vivo photothermal therapy efficiency. Moreover, QE-PEG-AgS has good photoacoustic imaging (PAI) ability; this QE-PEG-AgS concentration dependent signal can precisely follow the accumulation of the nanomaterials in tumors and dictate the correct time for light therapy. As a result, QE-PEG-AgS achieved complete tumor ablation effect with no recurrence when only irradiated with NIR light for 10 min. This approach offers a new approach for the theranostic applications of AgS NDs. STATEMENT OF SIGNIFICANCE: In this work, pH-responsive AgS nanodots loaded with the heat shock protein inhibitor for enhanced photothermal cancer therapy have been simply prepared via self-assembly process. This nanoagent possesses ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The acidic environment of tumor cells and the acidity of lysosomes, as well as the high temperature generated by photothermal therapy under irradiation of NIR light promote the release of the inhibitor molecules from the nanoagent to improve the in vivo photothermal therapy efficiency. Moreover, the photoacoustic imaging (PAI) of the nanoagent can precisely follow the accumulation of the nanomaterials in tumors and dictate the light therapy time to guarantee the complete tumor ablation effect with no recurrence.
经过热处理的癌细胞由于热休克蛋白（HSP）水平上调而具有耐热性，导致治疗效率低下且肿瘤消融效果不佳。在这项工作中，我们报道了负载有HSP70抑制剂的pH响应性硫化银纳米点（AgS NDs）（QE-PEG-AgS）用于增强光热癌症治疗。QE-PEG-AgS通过疏水性AgS NDs、两亲性pH响应性PEG-PAE聚合物和HSP70抑制剂槲皮素（QE）的自组装轻松制备而成。QE-PEG-AgS具有理想的水溶性和生物相容性，能快速进入细胞，并优先在细胞溶酶体中积累。肿瘤细胞的微酸性环境以及溶酶体的酸性，以及在近红外光（808 nm）照射下光热疗法产生的高温，促进了抑制剂分子的释放，从而降低癌细胞的耐热性并提高体内光热治疗效率。此外，QE-PEG-AgS具有良好的光声成像（PAI）能力；这种依赖于QE-PEG-AgS浓度的信号可以精确跟踪纳米材料在肿瘤中的积累情况，并确定光疗的正确时间。结果，仅用近红外光照射10分钟，QE-PEG-AgS就实现了完全的肿瘤消融效果且无复发。这种方法为硫化银纳米点的诊疗应用提供了一种新途径。重要性声明：在这项工作中，通过自组装过程简单制备了负载热休克蛋白抑制剂的pH响应性硫化银纳米点用于增强光热癌症治疗。这种纳米制剂具有理想的水溶性和生物相容性，能快速进入细胞，并优先在细胞溶酶体中积累。肿瘤细胞的酸性环境和溶酶体的酸性，以及近红外光照射下光热疗法产生的高温，促进了抑制剂分子从纳米制剂中释放出来，从而提高体内光热治疗效率。此外，该纳米制剂的光声成像（PAI）可以精确跟踪纳米材料在肿瘤中的积累情况，并确定光疗时间，以确保完全的肿瘤消融效果且无复发。
