Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun, China.
Nanoscale. 2021 May 21;13(19):8998-9008. doi: 10.1039/d0nr08024a. Epub 2021 May 11.
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA-DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA-DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA-DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.
程序性细胞死亡配体 1（PD-L1）阻断在癌症免疫治疗中取得了巨大成功。PD-L1 siRNA 通过下调肿瘤细胞 PD-L1 的水平，可以恢复 T 细胞的免疫抗肿瘤活性，但 PD-1/PD-L1 单药治疗的效率相对较低。阿霉素（DOX）可诱导肿瘤细胞凋亡，进而增加肿瘤抗原的释放。但是，DOX 处理的肿瘤组织中 PD-L1 的表达会适应性增强。因此，DOX 与 PD-L1 siRNA 联合使用可以产生良好的协同抗肿瘤作用。在这项研究中，构建了载有 DOX 和 PD-L1 siRNA 的干细胞膜（SCM）伪装的聚多巴胺纳米颗粒（PDA-DOX/siPD-L1@SCM），用于靶向前列腺癌（PCa）骨转移。PDA-DOX/siPD-L1@SCM NPs 能够有效地增强血液保留并提高肿瘤部位的积累。体外和体内研究表明，PDA-DOX/siPD-L1@SCM NPs 在协同化学免疫治疗 PCa 骨转移方面表现出优异的性能。因此，本研究为开发用于治疗前列腺癌骨转移的仿生多功能纳米颗粒提供了一种有效的策略。
