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多功能壳聚糖/多孔硅@金纳米复合水凝胶通过单次注射实现癌症的长期重复局部联合治疗

Multifunctional Chitosan/Porous Silicon@Au Nanocomposite Hydrogels for Long-Term and Repeatedly Localized Combinatorial Therapy of Cancer via a Single Injection.

作者信息

Xia Bing, Zhang Weiwei, Tong Haibei, Li Jiachen, Chen Zhenyu, Shi Jisen

机构信息

Key Laboratory of Forest Genetics & Biotechnology (Ministry of Education of China), Nanjing Forestry University, Nanjing 210037, P. R. China.

College of Science, Nanjing Forestry University, Nanjing 210037, P. R. China.

出版信息

ACS Biomater Sci Eng. 2019 Apr 8;5(4):1857-1867. doi: 10.1021/acsbiomaterials.8b01533. Epub 2019 Mar 29.

Abstract

Considering the future clinical applications of localized cancer therapy, it is of great importance to construct injectable biodegradable nanocomposite hydrogels with combinatorial therapeutic efficacy. Here, porous silicon nanoparticles (PSiNPs) as host matrix were chosen to fabricate PSiNPs@Au nanocomposites via reductive synthesis of gold nanoparticles. Then PSiNPs@Au nanocomposites were further incorporated into thermosensitive chitosan (CS) hydrogels to construct CS/PSiNPs@Au nanocomposite hydrogels, which showed gelation at physiological temperature, excellent biodegradability, and biocompatibility. Especially with the encapsulation of CS hydrogels, PSiNPs@Au nanocomposites had a long-term stable photothermal effect with higher local temperature under near-infrared (NIR) laser irradiation, whether or . Besides, assisted by NIR laser irradiation, CS/PSiNPs@Au nanocomposite hydrogels exhibited a long-term sustained release of anticancer drugs (doxorubicin hydrochloride, DOX) in acidic tumor environments. Finally, DOX/CS/PSiNPs@Au precursors were administrated into tumor-bearing mice via a single intratumoral injection, which presented a significant synergistic chemo-photothermal therapeutic efficacy under repeated NIR laser irradiation during long-term cancer treatments. Accordingly, we developed a novel strategy to prepare multifunctional CS/PSiNPs@Au nanocomposite hydrogels and also demonstrated their potential applications in localized cancer therapy in future clinics.

摘要

考虑到局部癌症治疗的未来临床应用,构建具有联合治疗效果的可注射可生物降解纳米复合水凝胶具有重要意义。在此,选择多孔硅纳米颗粒(PSiNPs)作为主体基质,通过金纳米颗粒的还原合成制备PSiNPs@Au纳米复合材料。然后将PSiNPs@Au纳米复合材料进一步掺入热敏壳聚糖(CS)水凝胶中,构建CS/PSiNPs@Au纳米复合水凝胶,该水凝胶在生理温度下表现出凝胶化、优异的生物降解性和生物相容性。特别是在CS水凝胶的包裹下,PSiNPs@Au纳米复合材料在近红外(NIR)激光照射下具有长期稳定的光热效应,局部温度更高,无论是否……此外,在NIR激光照射的辅助下,CS/PSiNPs@Au纳米复合水凝胶在酸性肿瘤环境中表现出抗癌药物(盐酸多柔比星,DOX)的长期持续释放。最后,通过单次瘤内注射将DOX/CS/PSiNPs@Au前体给药于荷瘤小鼠,在长期癌症治疗期间重复NIR激光照射下呈现出显著的协同化疗-光热治疗效果。因此,我们开发了一种制备多功能CS/PSiNPs@Au纳米复合水凝胶的新策略,并展示了它们在未来临床局部癌症治疗中的潜在应用。

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