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Ruthenium (II)-Coordinated Supramolecular Metallodrug Complex Realizing Oxygen Self-Supply In Situ for Overcoming Hypoxic Tumors
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2021-08-26 , DOI: 10.1002/adfm.202105837 Chengfei Liu 1 , Muqiong Li 2 , Pengxiang Li 1 , Yang Bai 3 , Jun Pang 4 , Li Fan 2 , Wei Tian 1
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2021-08-26 , DOI: 10.1002/adfm.202105837 Chengfei Liu 1 , Muqiong Li 2 , Pengxiang Li 1 , Yang Bai 3 , Jun Pang 4 , Li Fan 2 , Wei Tian 1
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Tumor hypoxia greatly limits the antitumor therapeutic efficacy of oxygen (O2)-dependent treatments. The common strategies of doping O2 generating compounds into one “package” may lead to insufficient O2 supply in situ in cancer cells due to the relatively low loading content, limited reproducibility, and uncontrollable release kinetics. Herein, organometallic drug complexes combined with a supramolecular interaction strategy are proposed to realize a stable and efficient O2 self-supply in situ for overcoming hypoxic tumors. A ruthenium (II)-coordinated supramolecular metallodrug complex (RuSMDC) is first designed and synthesized via host–guest interactions between two functionalized drug molecules, in which ruthenium is used to catalyze the decomposition of hydrogen peroxide to produce O2. The obtained RuSMDC further self-assembles into Ru-containing supramolecular metallodrug micelles (RuSMDMs), which provides sufficient O2 for chemotherapy and photodynamic therapy (PDT) oncotherapy in an anaerobic tumor environment. In vitro and in vivo studies further confirm that RuSMDMs effectively alleviate the tumor hypoxic environment, greatly improve the therapeutic effect of chemotherapy and PDT oncotherapy, and reduce the systemic toxicity to normal organs.
中文翻译：
钌 (II) 配位超分子金属药物复合物实现原位自供氧以克服缺氧肿瘤
肿瘤缺氧极大地限制了氧 (O 2 ) 依赖性治疗的抗肿瘤治疗功效。由于负载量相对较低、重现性有限和释放动力学不可控，将O 2生成化合物掺杂到一个“包装”中的常见策略可能会导致癌细胞中原位O 2供应不足。在此，提出了有机金属药物配合物结合超分子相互作用策略以实现稳定高效的 O 2原位自供以克服缺氧肿瘤。钌 (II) 配位的超分子金属药物复合物 (RuSMDC) 首先通过两个功能化药物分子之间的主客体相互作用设计和合成，其中钌用于催化过氧化氢分解以产生 O 2。获得的RuSMDC进一步自组装成含Ru的超分子金属药物胶束（RuSMDMs），为厌氧肿瘤环境中的化学疗法和光动力疗法（PDT）肿瘤疗法提供足够的O 2。体内外研究进一步证实，RuSMDMs有效缓解肿瘤缺氧环境，大大提高化疗和PDT肿瘤治疗的疗效，降低对正常器官的全身毒性。
更新日期：2021-08-26
中文翻译：
钌 (II) 配位超分子金属药物复合物实现原位自供氧以克服缺氧肿瘤
肿瘤缺氧极大地限制了氧 (O 2 ) 依赖性治疗的抗肿瘤治疗功效。由于负载量相对较低、重现性有限和释放动力学不可控，将O 2生成化合物掺杂到一个“包装”中的常见策略可能会导致癌细胞中原位O 2供应不足。在此，提出了有机金属药物配合物结合超分子相互作用策略以实现稳定高效的 O 2原位自供以克服缺氧肿瘤。钌 (II) 配位的超分子金属药物复合物 (RuSMDC) 首先通过两个功能化药物分子之间的主客体相互作用设计和合成，其中钌用于催化过氧化氢分解以产生 O 2。获得的RuSMDC进一步自组装成含Ru的超分子金属药物胶束（RuSMDMs），为厌氧肿瘤环境中的化学疗法和光动力疗法（PDT）肿瘤疗法提供足够的O 2。体内外研究进一步证实，RuSMDMs有效缓解肿瘤缺氧环境，大大提高化疗和PDT肿瘤治疗的疗效，降低对正常器官的全身毒性。
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