Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, P. R. China.
J Mater Chem B. 2020 Oct 21;8(40):9351-9361. doi: 10.1039/d0tb01692f.
Combined X-ray-induced photodynamic therapy (X-PDT) and chemotherapy are of great interest for tumor treatment, but their outcome is still hindered by insufficient drug delivery without tumor specificity and the difficulty of switching to chemotherapy during the X-PDT process. Herein, we report an efficient strategy for preparing a nanocarrier, DANPVP&DOX, with slight-acidity-induced charge conversion and hypoxia-motivated doxorubicin (DOX) release properties to achieve a more precise and synchronous therapeutic effect. Upon a change in the extracellular pH (pHe) in the tumor matrix, the surface charge of DANPVP&DOX converted from negative to positive via dimethyl maleate degradation. Following the increased internalization by tumoral cells, exposure of verteporfin (VP) in DANPVP&DOX to low-dose X-ray radiation resulted in O2 consumption in the cytoplasm to produce cytotoxic reactive oxygen species (ROS), which caused cell killing. Moreover, the hypoxic conditions formed in the tumor area specifically promoted DANPVP&DOX dissociation and on-demand DOX release. Consequently, DANPVP&DOX significantly increased the therapeutic efficacy through X-PDT and cascade chemotherapy. More importantly, this strategy could potentially be extended to various therapeutic agents other than anticancer drugs for precise drug delivery and cancer treatment.
联合 X 射线诱导的光动力疗法（X-PDT）和化学疗法在肿瘤治疗方面具有很大的吸引力，但由于缺乏肿瘤特异性的药物输送以及在 X-PDT 过程中难以切换到化学疗法，其效果仍然受到限制。在此，我们报告了一种有效的策略，用于制备纳米载体 DANPVP&DOX，该载体具有轻微酸性诱导的电荷转换和缺氧驱动的阿霉素（DOX）释放特性，以实现更精确和同步的治疗效果。当肿瘤基质中细胞外 pH（pHe）发生变化时，DANPVP&DOX 的表面电荷通过马来酸二甲酯降解从负电荷转变为正电荷。随后，肿瘤细胞内化增加后，DANPVP&DOX 中的维替泊芬（VP）暴露于低剂量 X 射线辐射下会导致细胞质中 O2 消耗，从而产生细胞毒性活性氧（ROS），导致细胞杀伤。此外，肿瘤区域形成的缺氧条件特异性促进 DANPVP&DOX 解离和按需 DOX 释放。因此，DANPVP&DOX 通过 X-PDT 和级联化疗显著提高了治疗效果。更重要的是，该策略可能会扩展到除抗癌药物以外的各种治疗剂，以实现精确的药物输送和癌症治疗。
