SO2 prodrug doped nanorattles with extra-high drug payload for "collusion inside and outside" photothermal/pH triggered - gas therapy
SO2 prodrug doped nanorattles with extra-high drug payload for "collusion inside and outside" photothermal/pH triggered - gas therapy
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DOI：
10.1016/j.biomaterials.2020.120236
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发表时间：
2020-10-01
期刊：
影响因子：
14
通讯作者：
Li, Nan
中科院分区：
文献类型：
--
作者：
Lu, Qianglan;Lu, Tong;Li, Nan
近年来，气体治疗纳米平台蓬勃发展，成为癌症治疗的一个有前景的领域。然而，气体产生不受控制或不充分以及治疗机制不明确，仍然被视为气体疗法应用于临床的巨大挑战。本文探索了一种基于二氧化硫（SO2）前药掺杂纳米摇铃的气体治疗方法，它不仅可以抑制浅表肿瘤，还可以抑制深部肿瘤。制备了由金纳米棒核和聚多巴胺（PDA）壳组成的苯并噻唑亚磺酸盐（BTS，一种水溶性SO2前药）掺杂的具有高药物负载（约80％）的拨浪鼓结构粗糙纳米胶囊（GNRs@PDA-BTS，GPBRs）。利用优异的光热转换能力以及肿瘤部位的酸性条件，SO2气体的释放可以通过光热和pH值精确控制，从而实现“内合”气体治疗和“外”光热治疗。此外，细胞毒性 SO2 被发现可诱导细胞凋亡，同时上调细胞内活性氧 (ROS) 水平并调节凋亡相关蛋白，如 p53、bcl-2、Bax 和 caspase-3。这种光热/pH触发的SO2气体疗法可能为刺激深部肿瘤治疗的进一步发展提供有效的策略。
Recent years have witnessed the blooming of gas therapy nanoplatforms, which emerged as a promising area for cancer therapy. However, uncontrolled or inadequate generation of gas and unclear therapeutic mechanisms, which were still regarded as big challenges to apply gas therapy into clinical. Here in, a gas treatment based on sulfur dioxide (SO2) prodrug doped nanorattles was explored, which could not only inhibit superficial tumor but also deep tumor. A Benzothiazole sulfinate (BTS, a water-soluble SO2 prodrug) doped rattle-structured rough nanocapsule with high drug payload (similar to 80%) composed of gold nanorods cores and polydopamine (PDA) shell (GNRs@PDA-BTS, GPBRs) has been prepared. Taking advantages of excellent photothermal conversion ability as well as acidic condition in the tumor sites, SO2 gas release could be precisely controlled by both photothermal and pH, thus realizing "collusion inside" gas therapy and "outside" photothermal therapy. In addition, the cytotoxic SO2 was found to induce cell apoptosis accompanied by the upregulation of intracellular reactive oxygen species (ROS) levels and modulation of apoptosis-relative proteins such as p53, bcl-2, Bax and caspase-3. Such photothermal/pH triggered SO2 gas therapy may provide an effective strategy to stimulate further development of deep tumor therapy.