Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, United States.
Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois 60637, United States.
Bioconjug Chem. 2021 Nov 17;32(11):2318-2326. doi: 10.1021/acs.bioconjchem.1c00362. Epub 2021 Oct 4.
Combination therapy enhances anticancer efficacy through synergistic effects of different drugs/modalities and can potentially address the challenges in the treatment of metastatic diseases. Here we report the design of carb/pyro nanoscale coordination polymer nanoparticles that carry carboplatin (carb) in the core and the photosensitizer pyrolipid (pyro) on the shell for the treatment of metastatic triple negative breast cancer. Upon light irradiation, carb/pyro generated reactive oxygen species to cause severe cell apoptosis and early calreticulin exposure. Upon intravenous injection and local light irradiation, carb/pyro significantly regressed tumor growth in the 4T1 murine metastatic breast cancer model. When combined with an anti-CD47 antibody, carb/pyro with light irradiation completely eradicated primary and metastatic 4T1 tumors in 50% mice. The anticancer efficacy of carb/pyro was also demonstrated in the CT26 murine colorectal cancer model.
联合治疗通过不同药物/模式的协同作用增强抗癌疗效,并可能解决转移性疾病治疗中的挑战。在这里,我们报告了载有顺铂(carb)核和光敏剂吡咯脂质(pyro)壳的碳/热纳米级配位聚合物纳米粒子的设计,用于治疗转移性三阴性乳腺癌。在光照下,carb/pyro 产生活性氧,导致严重的细胞凋亡和早期钙网蛋白暴露。静脉注射和局部光照后,carb/pyro 显著抑制了 4T1 鼠转移性乳腺癌模型中的肿瘤生长。当与抗 CD47 抗体联合使用时,carb/pyro 联合光照可使 50%的小鼠完全消除原发性和转移性 4T1 肿瘤。carb/pyro 的抗癌疗效也在 CT26 鼠结直肠癌模型中得到了证明。