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| 1 | 抑制癌症治疗多药耐药性的纳米药物递送体系显示文摘多药耐药(MDR)是指肿瘤细胞对传统和新型化疗药物产生耐药性的现象,成为治疗恶性肿瘤的重要障碍。近年来,已发现纳米药物递送体系(NDDS)在抑制肿瘤MDR方面表现出独特优势,可增加药物的溶解度和稳定性,避开药物外排泵、以更低的剂量和更少的副作用实现目标部位更高的药物浓度。因此,NDDS成为克服癌症MDR的有效策略。介绍了肿瘤MDR机制;从多肽类配体、叶酸靶向配体、转铁蛋白靶向配体、透明质酸配体、双配体及其他配体5个方面总结了辅助纳米粒子克服MDR的研究进展;综述了内源性及外源性刺激响应型纳米药物的设计、结构以及克服MDR的效果;提出了抑制癌症治疗多药耐药性的NDDS存在的问题及未来发展方向。 | 葛界芳 熊向源 | 2023 | 精细化工2023，40，5： | 2 |
| 2 | Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity显示文摘Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways.The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications.To circumvent this issue,we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle(PNM)for cancer therapy.PNM was engineered by integrating the PI3K/m TOR inhibitor PF-04691502(PF)and the broad spectrum CDK inhibitor flavopiridol(Flav)into a single nanoplatform,which showed tumor-specific accumulation,activation and deep penetration in response to the high glutathione(GSH)tumoral microenvironment.The codelivery of PF and Flav could trigger gasdermin E(GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response.Furthermore,the combination of PNM-induced immunogenic pyroptosis with antiprogrammed cell death-1(a PD-1)immunotherapy further boosted the antitumor effect and prolonged the survival time of mice.Collectively,these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/m TOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy. | Qichao Yang Xianbin Ma Yao Xiao Tian Zhang Leilei Yang Shaochen Yang Mengyun Liang Shuo Wang Zhizhong Wu Zhigang Xu Zhijun Sun | 2022 | Acta Pharmaceutica Sinica B2022，12，7： | 0 |
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