DataSheet1_Tumor Cell Distinguishable Nanomedicine Integrating Chemotherapeutic Sensitization and Protection.docx

Theoretically, with a high enough drug dosage, cancer cells could be eliminated. However, the dosages that can be administered are limited by the therapeutic efficacy and side effects of the given drug. Herein, a nanomedicine integrating chemotherapeutic sensitization and protection was developed to relieve the limitation of administration dosage and to improve the efficacy of chemotherapy. The nanomedicine was endowed with the function of synergistically controlled release of CO and drugs under near-infrared (NIR) light irradiation. CO photo-induced release system (COPIRS) was synthesized by constructing an electron excitation–electron transfer group–electron-induced CO release structure and was used as the hydrophobic part, and then hydrophilic polymer (polyethylene glycol; PEG) was introduced by a thermal-responsive groups (DA group), forming a near-infrared-induced burst-release nanocarrier. In vitro and in vivo experiments showed that the nanomedicine can distinguish between tumor and normal cells and regulates the resistance of these different cells through the controlled release of carbonic oxide (CO), simultaneously enhancing the efficacy of chemotherapy drugs on tumor cells and chemotherapeutic protection on normal cells. This strategy could solve the current limitations on dosages due to toxicity and provide a solution for tumor cure by chemotherapy.

理论上，提升药物剂量即可清除癌细胞，但临床可给药剂量受限于对应药物的治疗效力与毒副作用。为此，本研究开发了一种兼具化疗增敏与防护功能的纳米药物，以突破给药剂量限制并提升化疗疗效。该纳米药物可在近红外（near-infrared, NIR）光照射下，实现一氧化碳（carbonic oxide, CO）与化疗药物的协同控释。本研究通过构建电子激发-电子转移-电子诱导CO释放结构，合成了CO光诱导释放系统（CO photo-induced release system, COPIRS）并将其作为疏水段；随后通过温敏基团（DA group）引入亲水性聚合物聚乙二醇（polyethylene glycol, PEG），最终形成近红外触发的突释型纳米载体。体外与体内实验结果表明，该纳米药物可精准区分肿瘤细胞与正常细胞，并通过控释一氧化碳（carbonic oxide, CO）调控两类细胞的耐药性：同时增强化疗药物对肿瘤细胞的杀伤效力，以及对正常细胞的化疗防护作用。该策略可破解当前因药物毒性导致的给药剂量限制难题，为化疗实现肿瘤根治提供全新解决方案。