Light-activatable liposomes for repetitive on-demand drug release and immunopotentiation in hypoxic tumor therapy
Light-activatable liposomes for repetitive on-demand drug release and immunopotentiation in hypoxic tumor therapy
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光激活脂质体，用于缺氧肿瘤治疗中重复按需药物释放和免疫增强。
DOI：
10.1016/j.biomaterials.2020.120456
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发表时间：
2021-01-01
期刊：
影响因子：
14
通讯作者：
Yu, Zhiqiang
中科院分区：
文献类型：
--
作者：
Yang, Yuanyuan;Liu, Xin;Yu, Zhiqiang
具有理想的重复按需药物释放特征的外部刺激响应性纳米药物被认为可以极大地适应患者灵活的用药方案。为此目的，设计了整合有Ce 6光动力组分和四价铂前药（Pt（IV））化疗组分的光活化脂质体（Pt/Ce 6-LP）。该多功能系统采用不饱和磷脂进行合理设计，在间断光照射下实现重复按需释药，从而实现对缺氧肿瘤的化学-光动力治疗效应和免疫增强作用。此外，在从Pt（IV）前药转化为Pt（II）期间谷胱甘肽（GSH）的消耗可以避免光动力疗法（PDT）中活性氧（ROS）的耗尽。注意，这种正反馈回路似乎重塑了肿瘤中H2 O2和GSH的氧化还原平衡，缓解了缺氧的肿瘤微环境。减轻缺氧被认为是至关重要的增强PDT疗效，逆转顺铂耐药的肿瘤，和极化的肿瘤相关的巨噬细胞（TAM）的免疫活性M1-表型。光照射Pt/Ce 6-LP在肝细胞癌的患者源性肿瘤异种移植模型中显示出显著的抗肿瘤作用和持续的给药后抑制。
External stimuli-responsive nanomedicine with desirable repetitive on-demand drug release character is postulated to greatly accommodate patients' flexible medication regime. To this object, light-activatable liposomes (Pt/Ce6-LP) integrated with both a Ce6 photodynamic component and a tetravalent platinum prodrug (Pt(IV)) chemotherapeutic component are engineered. This multifunctional system was rationally designed using unsaturated phospholipid to achieve repetitive on-demand drug release under discontinuous light irradiation, thus performing chemo-photodynamic therapy effect and immunopotentiation in hypoxic tumor. Furthermore, glutathione (GSH) consumption during transformation from Pt(IV) prodrug to Pt(II) can avoid depletion of reactive oxygen species (ROS) in photodynamic therapy (PDT). Note this positive feedback loop appears to remodel the redox balance of H2O2 and GSH in tumors, alleviating the hypoxic tumor microenvironment. The alleviated hypoxia is found to be critical to the enhancement of PDT efficacy, reversal of cisplatin resistance in tumors, and polarization of tumor-associated macrophages (TAMs) to the immunocompetent M1-phynotype. Pt/Ce6-LP with light radiation demonstrates significant antitumor effect and persistent post-medication inhibition in patient-derived tumor xenograft model of hepatocellular carcinoma.