In this work, a traceable dual-porous mesoporous silica-coated mesoporous carbon nanocomposite (MCN@Si) with high drug loading capacity and high photothermal conversion efficiency (30.5 %) was successfully prepared. Based on the nanocomposite, a pH/redox/near infrared (NIR) multi-stimuli responsive drug delivery system was constructed to realize the accurate drug delivery, drug controlled release and chemo-photothermal synergistic antitumor therapy. MCN@Si was used as a vehicle to load doxorubicin (DOX) with a high drug loading efficacy of 48.2 % and a NIR absorbance agent for photothermal therapy and NIR thermal imaging. Carbon dots (CDs) with proper size were covalently attached to the surface of MCN@Si via disulfide bonds to block the mesopores, preventing DOX premature release from DOX/MCN@Si-CDs. Besides, CDs were served as fluorescent probe to prove the visualization potential of the drug delivery system. DOX was rapidly released at the condition of low pH and high GSH concentration due to the breakage of disulfide bonds and protonation of DOX. Moreover, the local hyperthermia generated by MCN@Si-CDs under NIR irradiation could not only directly kill cells, but also accelerate DOX release and enhance cells sensitivity and permeability. Two-dimensional cells and three-dimensional tumor spheroids assays illustrated that DOX/MCN@Si-CDs + NIR group exhibited a superior thermochemotherapy synergistic treatment effect and the combination index (CI) was 0.378. Biodistribution study showed the biosecurity of preparations and its prolonged detention time in tumor sites. Besides, antitumor experiment in vivo also performed the excellent synergistic inhibition effect. All the results demonstrated that DOX/MCN@Si-CDs is a traceable multi-stimuli responsive nanodelivery system and can achieve efficient chemo-photothermal synergistic antitumor therapy.

在这项工作中，成功地制备了具有高载药量和高光热转化效率（30.5％）的可追溯的双孔介孔二氧化硅涂层介孔碳纳米复合材料（MCN @ Si）。基于纳米复合材料，构建了pH /氧化还原/近红外（NIR）多刺激响应药物递送系统，以实现准确的药物递送，药物控释和化学-光热协同抗肿瘤治疗。MCN @ Si被用作载有阿霉素（DOX）的载体，具有48.2％的高载药效率，以及用于光热疗法和NIR热成像的NIR吸收剂。尺寸合适的碳点（CD）通过MCN @ Si表面共价连接二硫键可阻断中孔，防止DOX从DOX / MCN @ Si-CD中过早释放。此外，CD还用作荧光探针，以证明药物输送系统的可视化潜力。由于二硫键的断裂和质子化，DOX在低pH和高GSH浓度下迅速释放。此外，MCN @ Si-CDs在近红外辐射下产生的局部高温不仅可以直接杀死细胞，而且可以加速DOX的释放并增强细胞的敏感性和通透性。二维细胞和三维肿瘤球体分析表明，DOX / MCN @ Si-CDs + NIR组具有更好的热化学协同治疗效果，组合指数（CI）为0.378。生物分布研究表明制剂的生物安全性及其在肿瘤部位的延长滞留时间。此外，抗肿瘤实验体内也表现出优异的协同抑制作用。所有结果表明，DOX / MCN @ Si-CDs是可追溯的多刺激响应性纳米递送系统，可以实现有效的化学-光热协同抗肿瘤治疗。