Specific-oxygen-supply functionalized core-shell nanoparticles for smart mutual-promotion between photodynamic therapy and gambogic acid-induced chemotherapy
Specific-oxygen-supply functionalized core-shell nanoparticles for smart mutual-promotion between photodynamic therapy and gambogic acid-induced chemotherapy
复制标题
特定供氧功能化核壳纳米粒子用于光动力疗法和藤黄酸诱导化疗之间的智能互促进。
DOI：
10.1016/j.biomaterials.2020.120228
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发表时间：
2020-10-01
期刊：
影响因子：
14
通讯作者：
Xue, Jingwei
中科院分区：
文献类型：
--
作者：
Han, Lingfei;Wang, Yingming;Xue, Jingwei
光动力疗法（PDT）和癌症化疗都面临着各自的挑战。肿瘤缺氧、低渗透和高谷胱甘肽（GSH）水平首当其冲。在此基础上，构建了一种具有低氧响应、特定供氧和深度穿透肿瘤等多功能的核壳纳米粒子，实现了两者之间的智能互促，克服了各自的限制。该纳米平台（GC@MCS NPs）由低氧响应透明质酸-硝基咪唑（HA-NI）为壳层，MnO2 NPs为氧调节剂，还原响应功能化聚l -谷氨酸衍生物（γ - pfga）为核心组成，可传递甘草酸（GA）和氯6 （Ce6）。内吞后，大约100 nm的GC@MCS NPs实现缺氧响应壳降解和MnO2释放，然后进行还原激活的电荷转换，形成带正电的核。部分释放的GA对浅表肿瘤细胞有损伤作用，负载ga&ce6的γ - pfga通过电子相互作用逐步深入肿瘤细胞内部。在638 nm的激光照射下，广泛渗透的Ce6在MnO2 NPs的高氧作用下被激活以增强PDT。生成的活性氧（ROS）反过来通过清除高水平的谷胱甘肽促进ga诱导的细胞凋亡。因此，这种相互促进策略对4T1肿瘤抑制率的贡献率为92.41%，优势突出。我们的GC@MCS NPs提供了一种化学光动力治疗的智能组合，专注于解决肿瘤缺氧和低穿透问题。
Photodynamic therapy (PDT) and chemotherapy of cancer both meet respective challenges. Tumor hypoxia, low penetration and high glutathione (GSH) level bear the brunt. Herein, a core-shell nanoparticle, with multi-function of hypoxia-responsiveness, specific oxygen supply and deep tumor penetration, was constructed for smart mutual-promotion between the both to overcome the respective restrictions. The nano platform (GC@MCS NPs) was composed of hypoxia-responsive hyaluronic acid-nitroimidazole (HA-NI) as shells, MnO2 NPs as oxygen modulators and reduction-responsive functionalized poly (L-glutamic acid) derivatives (gamma-PFGA) as cores to deliver gambogic acid (GA) and Chlorine6 (Ce6). After endocytosis, the approximately 100 nm of GC@MCS NPs achieved hypoxia-responsive shell degradation and MnO2 release, followed by reduction-activated charge conversion to form positively charged cores. With the damage effect of superficial tumor cells by the partially released GA, GA&Ce6-loaded gamma-PFGA penetrated deep inside through electronic interaction step by step. Upon irradiated with 638 nm of laser, widely permeated Ce6 was activated for enhanced PDT under the high oxygenation by MnO2 NPs. The generated reactive oxygen species (ROS) in return facilitated the GA-induced paraptosis by clearing high level of GSH. As a result, this mutual promotion strategy contributed to 92.41% of 4T1 tumor inhibition rate, exhibiting outstanding advantages. Our GC@MCS NPs provided a smart combination of chemo-photodynamic therapy and focused on addressing the tumor hypoxia and low penetration issues.