PDF(Pubmed)
Abstract：
UNASSIGNED: Immune regulatory small molecule JQ1 can block its downstream effector PD-L1 pathway and effectively reverse the PD-L1 upregulation induced by doxorubicin (DOX). So the synergistic administration of chemotherapeutic drug DOX and JQ1 is expected to increase the sensitivity of tumors to immune checkpoint therapy and jointly enhance the body\'s own immunity, thus effectively killing tumor cells. Therefore, a drug delivery system loaded with DOX and JQ1 was devised in this study.
UNASSIGNED: Polydopamine nanoparticles (PDA NPs) were synthesized through spontaneous polymerization. Under appropriate pH conditions, DOX and JQ1 were loaded onto the surface of PDA NPs, and the release of DOX and JQ1 were measured using UV-Vis or high performance liquid chromatography (HPLC). The mechanism of fabricated nanocomplex in vitro was investigated by cell uptake experiment, cell viability assays, apoptosis assays, and Western blot analysis. Finally, the tumor-bearing mouse model was used to evaluate the tumor-inhibiting efficacy and the biosafety in vivo.
UNASSIGNED: JQ1 and DOX were successfully loaded onto PDA NPs. PDA-DOX/JQ1 NPs inhibited the growth of prostate cancer cells, reduced the expression of apoptosis related proteins and induced apoptosis in vitro. The in vivo biodistribution indicated that PDA-DOX/JQ1 NPs could accumulated at the tumor sites through the EPR effect. In tumor-bearing mice, JQ1 delivered with PDA-DOX/JQ1 NPs reduced PD-L1 expression at tumor sites, generating significant tumor suppression. Furthermore, PDA-DOX/JQ1 NPs could reduce the side effects, and produce good synergistic treatment effect in vivo.
UNASSIGNED: We have successfully prepared a multifunctional platform for synergistic prostate cancer therapy.
UNASSIGNED: Polydopamine nanoparticles (PDA NPs) were synthesized through spontaneous polymerization. Under appropriate pH conditions, DOX and JQ1 were loaded onto the surface of PDA NPs, and the release of DOX and JQ1 were measured using UV-Vis or high performance liquid chromatography (HPLC). The mechanism of fabricated nanocomplex in vitro was investigated by cell uptake experiment, cell viability assays, apoptosis assays, and Western blot analysis. Finally, the tumor-bearing mouse model was used to evaluate the tumor-inhibiting efficacy and the biosafety in vivo.
UNASSIGNED: JQ1 and DOX were successfully loaded onto PDA NPs. PDA-DOX/JQ1 NPs inhibited the growth of prostate cancer cells, reduced the expression of apoptosis related proteins and induced apoptosis in vitro. The in vivo biodistribution indicated that PDA-DOX/JQ1 NPs could accumulated at the tumor sites through the EPR effect. In tumor-bearing mice, JQ1 delivered with PDA-DOX/JQ1 NPs reduced PD-L1 expression at tumor sites, generating significant tumor suppression. Furthermore, PDA-DOX/JQ1 NPs could reduce the side effects, and produce good synergistic treatment effect in vivo.
UNASSIGNED: We have successfully prepared a multifunctional platform for synergistic prostate cancer therapy.
摘要：
■免疫调节小分子JQ1可以阻断其下游效应子PD-L1途径，并有效逆转多柔比星（DOX）诱导的PD-L1上调。因此，化疗药物DOX和JQ1的协同给药有望提高肿瘤对免疫检查点治疗的敏感性，共同增强机体自身的免疫力，从而有效地杀死肿瘤细胞。因此,本研究设计了一种装载DOX和JQ1的给药系统。
■通过自发聚合合成了聚多巴胺纳米颗粒（PDANP）。在适当的pH条件下，将DOX和JQ1加载到PDANP的表面上，使用UV-Vis或高效液相色谱法(HPLC)测量DOX和JQ1的释放。通过细胞摄取实验研究了体外制备纳米复合物的机理，细胞活力测定，凋亡测定，和蛋白质印迹分析。最后,荷瘤小鼠模型用于评估体内抑瘤效果和生物安全性。
■JQ1和DOX已成功加载到PDANP上。PDA-DOX/JQ1NP抑制前列腺癌细胞的生长，降低凋亡相关蛋白的表达,诱导细胞凋亡。体内生物分布表明，PDA-DOX/JQ1NP可以通过EPR效应在肿瘤部位积累。在荷瘤小鼠中，JQ1与PDA-DOX/JQ1NP一起降低了肿瘤部位的PD-L1表达，产生显著的肿瘤抑制。此外，PDA-DOX/JQ1NP可以减少副作用，并在体内产生良好的协同治疗效果。
■我们已经成功地制备了用于协同前列腺癌治疗的多功能平台。
■通过自发聚合合成了聚多巴胺纳米颗粒（PDANP）。在适当的pH条件下，将DOX和JQ1加载到PDANP的表面上，使用UV-Vis或高效液相色谱法(HPLC)测量DOX和JQ1的释放。通过细胞摄取实验研究了体外制备纳米复合物的机理，细胞活力测定，凋亡测定，和蛋白质印迹分析。最后,荷瘤小鼠模型用于评估体内抑瘤效果和生物安全性。
■JQ1和DOX已成功加载到PDANP上。PDA-DOX/JQ1NP抑制前列腺癌细胞的生长，降低凋亡相关蛋白的表达,诱导细胞凋亡。体内生物分布表明，PDA-DOX/JQ1NP可以通过EPR效应在肿瘤部位积累。在荷瘤小鼠中，JQ1与PDA-DOX/JQ1NP一起降低了肿瘤部位的PD-L1表达，产生显著的肿瘤抑制。此外，PDA-DOX/JQ1NP可以减少副作用，并在体内产生良好的协同治疗效果。
■我们已经成功地制备了用于协同前列腺癌治疗的多功能平台。
