Deng Bin, Ke Binghu, Tian Qixing, Gao Yukui, Zhai Qiliang, Zhang Wenqiang
Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.
Department of Science and Technology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.
J Nanobiotechnology. 2024 Dec 30;22(1):803. doi: 10.1186/s12951-024-03070-7.
Castration-resistant prostate cancer (CRPC) presents significant therapeutic challenges due to its aggressive nature and poor prognosis. Targeting Aurora-A kinase (AURKA) has shown promise in cancer treatment. This study investigates the efficacy of ART-T cell membrane-encapsulated AMS@AD (CM-AMS@AD) nanoparticles (NPs) in a photothermal-chemotherapy-immunotherapy combination for CRPC. Bioinformatics analysis of the Cancer Genome Atlas-prostate adenocarcinoma (TCGA-PRAD) dataset revealed overexpression of AURKA in PCa, correlating with poor clinical outcomes. Single-cell RNA sequencing data from the GEO database showed a significant reduction in immune cells in CRPC. Experimentally, T cell membrane-biomimetic NPs loaded with the AURKA inhibitor Alisertib and chemotherapy drug DTX were synthesized and characterized by dynamic light scattering and transmission electron microscopy, showing good stability and uniformity (average diameter: 158 nm). In vitro studies demonstrated that these NPs inhibited CRPC cell proliferation, increased the G2/M cell population, and elevated apoptosis, confirmed by γH2AX expression. In vivo, CM-AMS@AD NPs accumulated in tumor tissues, significantly slowed tumor growth, decreased proliferation, increased apoptosis, and improved the immune environment, enhancing dendritic cell (DC) maturation and increasing CD8 + /CD4 + ratios. These findings suggest that CM-AMS@AD NPs offer a promising triple-combination therapy for CRPC, integrating photothermal, chemotherapy, and immunotherapy, with significant potential for future clinical applications.
去势抵抗性前列腺癌（CRPC）因其侵袭性和预后不良而带来重大治疗挑战。靶向极光激酶A（AURKA）在癌症治疗中已显示出前景。本研究调查了ART-T细胞膜包裹的AMS@AD（CM-AMS@AD）纳米颗粒（NPs）在CRPC光热化疗-免疫治疗联合疗法中的疗效。对癌症基因组图谱-前列腺腺癌（TCGA-PRAD）数据集的生物信息学分析显示，AURKA在前列腺癌中过表达，与不良临床结果相关。来自基因表达综合数据库（GEO）的单细胞RNA测序数据显示，CRPC中的免疫细胞显著减少。实验中，合成了负载AURKA抑制剂阿利西替尼和化疗药物多西他赛（DTX）的T细胞膜仿生NPs，并通过动态光散射和透射电子显微镜进行表征，显示出良好的稳定性和均匀性（平均直径：158nm）。体外研究表明，这些NPs抑制CRPC细胞增殖，增加G2/M期细胞比例，并通过γH2AX表达证实提高了细胞凋亡率。在体内，CM-AMS@AD NPs在肿瘤组织中蓄积，显著减缓肿瘤生长，降低增殖，增加凋亡，并改善免疫环境，增强树突状细胞（DC）成熟并提高CD8+/CD4+比率。这些发现表明，CM-AMS@AD NPs为CRPC提供了一种有前景的三联疗法，整合了光热、化疗和免疫治疗，具有巨大的未来临床应用潜力。
