PCFM Lab of Ministry of Education and Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, PR China.
Research Lab for Biomedical Optics and Molecular Imaging, Shenzhen Key Lab for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
Acta Biomater. 2022 Jan 1;137:238-251. doi: 10.1016/j.actbio.2021.10.009. Epub 2021 Oct 12.
Semiconducting polymer (SP) is a promising photothermal agent in the antitumor application, but the co-delivery of the second near-infrared window (NIR-II)-based SPs with chemotherapeutic drug (e.g., doxorubicin (DOX)) remains a challenge. Here, SPs were firstly improved via backbone and alkyl side-chain engineering, and afterward, SPs and pH-sensitive prodrug copolymer self-assembled into a nanoparticle for a photoacoustic (PA)-imaging guided combination of photothermal therapy and chemotherapy. SP-encapsulated nanoparticles exhibited a high photothermal conversion efficiency of 45% at a relatively low power level of NIR irradiation (0.3 W/cm for 5 min). DOX was rapidly released in response to the acidic lysosomal environment. PA and fluorescence imaging confirmed that the photothermal therapy effectively drove DOX penetration inside tumor tissue, and it resulted in the killing of the surviving tumor cells from hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo. Overall, the co-delivery of the SP and DOX using pH-sensitive nanoparticles represents a feasible strategy for photothermal therapy with potentially synergistic drug effects. STATEMENT OF SIGNIFICANCE: Recent years have yielded great progress in semiconducting polymers (SPs)-based photothermal therapy for anticancer treatment. However, studies about molecular weight and side-chain of SPs on photothermal conversion efficiency are limited, and investigation of controlled codelivery with chemotherapeutic drug is lacking. Here, we improved the SPs performance via backbone and side-chain engineering, and afterward offered a pH-sensitive DOX-conjugated amphiphilic copolymer to encapsulate SPs. SP-encapsulated nanoparticles exhibited high photothermal conversion efficiency at a clinically feasible power level of NIR irradiation. NIR irradiation-generated hyperthermia not only killed tumor cells but also promoted DOX penetration inside the tumor tissue to ablate the tumor cells that survived hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo.
半导体聚合物（SP）是抗肿瘤应用中很有前途的光热试剂，但将第二个近红外窗口（NIR-II）基 SP 与化疗药物（例如阿霉素（DOX））共递仍然是一个挑战。在这里，通过主链和烷基侧链工程首先对 SP 进行了改进，然后将 SP 和 pH 敏感前药共聚物自组装成纳米颗粒，用于光声（PA）成像引导的光热治疗和化学疗法的联合治疗。在相对较低的 NIR 照射功率水平（NIR 照射 5 分钟，功率 0.3 W/cm）下，SP 封装的纳米颗粒表现出 45%的高光热转换效率。在酸性溶酶体环境中，DOX 迅速释放。PA 和荧光成像证实，光热疗法有效地将 DOX 驱动渗透到肿瘤组织内部，从而导致高温杀死存活的肿瘤细胞。体内验证了基于 SP 的光热疗法和 DOX 诱导的化疗的协同作用。总的来说，使用 pH 敏感纳米颗粒共递 SP 和 DOX 代表了一种具有潜在协同药物作用的光热治疗的可行策略。
近年来，基于半导体聚合物（SP）的光热疗法在癌症治疗方面取得了很大进展。然而，关于 SP 的分子量和侧链对光热转换效率的影响的研究还很有限，并且缺乏对与化疗药物的控制共递的研究。在这里，我们通过主链和侧链工程改进了 SP 的性能，然后提供了一种 pH 敏感的 DOX 缀合两亲性共聚物来封装 SP。SP 封装的纳米颗粒在临床可行的 NIR 照射功率水平下表现出高光热转换效率。NIR 照射产生的热不仅杀死了肿瘤细胞，还促进了 DOX 渗透到肿瘤组织内部，杀死了高温幸存的肿瘤细胞。体内验证了基于 SP 的光热疗法和 DOX 诱导的化疗的协同作用。
