Yang Yuming, Xu Minjie, Wang Zhe, Yang Yanqing, Liu Jie, Hu Qinglian, Li Lin, Huang Wei
Key Laboratory of Flexible Electronics (KLOFE) Institute of Advanced Materials (IAM), Nanjing Tech University, Nanjing 211800, China.
J Mater Chem B. 2021 Mar 21;9(11):2613-2622. doi: 10.1039/d0tb02903c. Epub 2021 Mar 8.
Photothermal therapy (PTT) based on semiconducting polymer nanoparticles (SPNs) is a promising strategy to treat solid tumors, but its ability to combine with chemotherapy for immune remodeling to efficiently suppress metastatic cancers has rarely been studied. Here, we demonstrate that PTT combined with chemotherapy can efficiently elicit immunity to suppress metastatic tumor growth. Specifically, we rationally designed a new SPN (PDPSe NPs) as a photothermal agent for PTT with a large mass extinction coefficient in the near-infrared region (e.g., 44.9 L g cm at 808 nm), high photothermal conversion efficiency (62.5%) and excellent biocompatibility. A hypoxia-activated anti-tumor drug, tirapazamine (TPZ), was selected for chemotherapy. Strikingly, the combination therapy not only induced tumor cell death in the primary tumor, but also effectively suppressed the growth of distant tumors (mimicking metastatic tumors) without PTT. Importantly, the combined therapies exhibit synergistic effects on immune remodeling. Immunofluorescence data suggest that the inhibition of metastatic tumor growth is attributed to the immune remodeling triggered by PTT and chemotherapy. This work demonstrates a new paradigm of utilizing PTT together with hypoxia-activated drugs to effectively retard metastatic tumor growth.
基于半导体聚合物纳米颗粒(SPNs)的光热疗法(PTT)是一种治疗实体瘤的有前景的策略,但其与化疗联合用于免疫重塑以有效抑制转移性癌症的能力鲜有研究。在此,我们证明PTT与化疗联合可有效激发免疫反应以抑制转移性肿瘤生长。具体而言,我们合理设计了一种新型SPN(PDPSe NPs)作为PTT的光热剂,其在近红外区域具有较大的质量消光系数(例如,在808 nm处为44.9 L g cm)、高光热转换效率(62.5%)和优异的生物相容性。选择了一种缺氧激活的抗肿瘤药物替拉帕米(TPZ)用于化疗。引人注目的是,联合疗法不仅在原发性肿瘤中诱导肿瘤细胞死亡,还能在不进行PTT的情况下有效抑制远处肿瘤(模拟转移性肿瘤)的生长。重要的是,联合疗法在免疫重塑方面表现出协同作用。免疫荧光数据表明,转移性肿瘤生长的抑制归因于PTT和化疗触发的免疫重塑。这项工作展示了一种利用PTT与缺氧激活药物有效延缓转移性肿瘤生长的新范例。
ACS Appl Mater Interfaces. 2024-8-7