Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.
Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, #08-03, Singapore, 138634, Singapore.
Adv Healthc Mater. 2019 Aug;8(15):e1900406. doi: 10.1002/adhm.201900406. Epub 2019 Jun 11.
Rational design of controllable drug release systems is important for tumor treatments due to the nonspecific toxicity of many chemotherapeutics. Herein, laser or light responsive pharmaceutical delivery nanoparticles are designed, by taking the advantages of redox responsive selenium (Se) substituted polymer as shell and photosensitive porphyrin zirconium metal-organic frameworks (MOF) as core. In detail, redox cleavable di-(1-hydroxylundecyl) selenide (DH-Se), biocompatible poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) are randomly polymerized to form poly(DH-Se/PEG/PPG urethane), which is used to coat the reactive oxygen species' (ROS) producible porous porphyrin zirconium metal organization formulation (PCN-224 MOF) to form the final poly(DH-Se/PEG/PPG urethane)@MOF shell-core nanoparticle with spherical shape by emulsion approach. Interestingly, poly(DH-Se/PEG/PPG urethane)@MOF nanoparticles with loading of chemotherapeutic doxorubicin (DOX) experience a fast and controllable release, which can realize the combination of chemotherapy and photodynamic therapy upon irradiation with laser light, due to the light-triggered ROS production by MOF which further causes the cleavage of poly(DH-Se/PEG/PPG urethane) polymer chain and the release of encapsulated DOX. To the best of the authors' knowledge, this is the first design of utilizing MOF and selenium substituted polymer as controllable drug release carriers, which might be beneficial for precise chemotherapy and photodynamic therapy combination.
由于许多化疗药物具有非特异性毒性，因此设计可控药物释放系统对于肿瘤治疗非常重要。在此，通过利用氧化还原响应硒（Se）取代聚合物作为壳和光敏卟啉锆金属-有机骨架（MOF）作为核的优势，设计了激光或光响应药物传递纳米粒子。具体而言，氧化还原可裂解二-（1-羟基十一烷基）硒化物（DH-Se）、生物相容性聚（乙二醇）（PEG）和聚（丙二醇）（PPG）随机聚合形成聚（DH-Se/PEG/PPG 氨酯），其用于涂覆可产生活性氧物质（ROS）的多孔卟啉锆金属组织制剂（PCN-224 MOF），通过乳液法形成最终的聚（DH-Se/PEG/PPG 氨酯）@MOF 核壳纳米粒子，其具有球形。有趣的是，负载化疗药物阿霉素（DOX）的聚（DH-Se/PEG/PPG 氨酯）@MOF 纳米粒子具有快速和可控的释放，这可以实现化疗和光动力治疗的结合，因为 MOF 引发的光触发 ROS 产生进一步导致聚（DH-Se/PEG/PPG 氨酯）聚合物链的裂解和封装的 DOX 的释放。据作者所知，这是首次利用 MOF 和硒取代聚合物作为可控药物释放载体的设计，这可能有利于精确的化疗和光动力治疗结合。
