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1小分子自组装纳米递药系统研究进展显示文摘生物纳米技术在药物递送领域的应用为高端创新制剂的研发注入了新动力,一系列新型纳米递药系统被相继开发乃至应用于临床。其中,由小分子药物或前药自组装形成的纳米递药系统因具有制备工艺简便、载药量超高和易于实现工业化生产等优势而备受关注,已成为纳米递药系统领域的一个重要分支。本文总结了小分子自组装纳米递药系统的最新研究进展。首先,对小分子前药自组装纳米递药系统进行介绍,包括两亲性、疏水性和二聚体小分子前药自组装纳米递药系统。其次,分别介绍小分子化学药物和小分子生物药物自组装纳米递药系统的最新进展。再者,对小分子杂化共组装纳米递药系统进行总结和分析,包括小分子纯药共组装纳米递药系统、小分子前药共组装纳米递药系统及小分子前药/小分子纯药共组装纳米递药系统。最后,讨论了小分子自组装纳米递药系统的合理设计、应用前景和临床挑战,以期为新一代纳米制剂的设计与构建提供参考。刘雨婷 王悦全 张申武 罗聪 2023药学学报2023,58,3:1
2Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy显示文摘As a promising modality for cancer therapy, photodynamic therapy(PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin(BSA-MHI148) and multi-kinase inhibitor Sorafenib(SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms:(i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory.(ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows:(i) Enhanced immunogenic cell death(ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species(ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability.(ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSAMHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.Zaigang Zhou Jiashe Chen Yu Liu Chunjuan Zheng Wenjuan Luo Lele Chen Shen Zhou Zhiming Li Jianliang Shen 2022Acta Pharmaceutica Sinica B2022,12,11:0
3纳米药物递送系统应用于肿瘤免疫治疗的研究进展显示文摘癌症免疫治疗是一种倍受关注的治疗策略。然而,免疫治疗面临的主要挑战包括患者反应性低、肿瘤特异性差、存在免疫抑制性肿瘤微环境等。纳米药物递送系统(nano drug delivery systems,NDDS)被用于负载药物,经修饰后可表现出肿瘤靶向性给药、肿瘤微环境响应和位点特异性释放等优异性能。因此,NDDS可以被有效地用于癌症免疫治疗,能减少毒副作用和免疫相关抑制。本文重点介绍了近来基于NDDS的免疫治疗的研究进展,包括诱导免疫原性细胞死亡(immunogenic cell death,ICD)、联合肿瘤免疫检查点抑制剂促进免疫治疗疗效、改善肿瘤免疫抑制微环境3个方面。杨逸博 李健 2023广东药科大学学报2023,39,4:0
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