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Abstract：
Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.
摘要：
三阴性乳腺癌(TNBC)具有低免疫细胞浸润的特点,高表达肿瘤程序性死亡配体1（PD-L1），和丰富的癌症干细胞。由于药物选择性差，传统化疗药物的全身毒性，和化疗失败由于肿瘤耐药等问题，因此，寻找治疗方案有限的TNBC的新癌症治疗策略尤为重要。抗肿瘤天然药物姜黄素和人参皂苷Rg3均可通过诱导肿瘤细胞免疫原性死亡(ICD)发挥抗肿瘤作用,减少PD-L1表达，减少癌症干细胞。然而,它们的缺点是水溶性差，低生物利用度，单药抗肿瘤作用较弱。我们使用乙烯基醚键将姜黄素（Cur）与N-O型两性离子聚合物连接，同时包封人参皂苷Rg3，以获得具有pH响应的超支化两性离子载药胶束OPDEA-PGED-5HA@Cur@Rg3（PPH@CR）。体外细胞实验和体内动物实验证明，PPH@CR不仅可以促进树突状细胞（DCs）的成熟，通过诱导肿瘤细胞ICD增加CD4+T细胞和CD8+T细胞，而且可以降低肿瘤组织中PD-L1的表达。和减少肿瘤干细胞，显示出更好的抗肿瘤效果和良好的生物安全性，这是一种有前途的癌症治疗策略。
