Three-pronged attacks by hybrid nanoassemblies involving a natural product, carbon dots, and Cu2+ for synergistic HCC therapy.
Three-pronged attacks by hybrid nanoassemblies involving a natural product, carbon dots, and Cu2+ for synergistic HCC therapy.
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DOI：
10.1016/j.jcis.2023.06.074
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发表时间：
2023-06
影响因子：
9.9
通讯作者：
Chun-Mei Lai;Jia Xu;Bingchen Zhang;Dong-Miao Li;Jiangwen Shen;Shi-Jing Yu;Jing-Wei Shao
中科院分区：
文献类型：
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作者：
Chun-Mei Lai;Jia Xu;Bingchen Zhang;Dong-Miao Li;Jiangwen Shen;Shi-Jing Yu;Jing-Wei Shao
肿瘤微环境（TME）刺激响应纳米组件正在成为有前途的药物递送系统（DDS），它在外源刺激下通过结构转变获得受控释放。然而，设计与纳米材料集成的智能刺激响应纳米平台以实现完全肿瘤消融仍然具有挑战性。因此，开发基于 TME 的刺激响应 DDS 以增强肿瘤部位的药物靶向递送和释放至关重要。在此，我们提出了一种有吸引力的策略，通过组装光敏剂（PS）、碳点（CD）、化疗剂熊果酸（UA）和铜离子（Cu2+）来构建荧光介导的TME刺激响应纳米平台，用于协同癌症治疗。首先，通过UA自组装制备UA纳米颗粒（UA NPs），然后UA NPs与CD通过氢键力组装得到UC NPs。与 Cu2+ 结合后，所得颗粒（称为 UCCu2+NPs）由于 UC NPs 的聚集而表现出猝灭的荧光和光敏性。进入肿瘤组织后，UCCu2+ 的光动力疗法 (PDT) 和荧光功能在 TME 刺激下恢复。 Cu2+的引入触发了UCCu2+NPs的电荷反转，从而促进溶酶体逃逸。此外，Cu2+通过与过氧化氢（H2O2）反应以及通过氧化还原反应消耗癌细胞中的谷胱甘肽（GSH）而产生额外的化学动力学治疗（CDT）能力，从而放大细胞内氧化应激并增强活性氧（ROS）疗法的治疗效果。综上所述，UCCu2+NPs通过三管齐下（化疗、光疗和热强化CDT）攻击实现协同治疗，为提高治疗效果提供了前所未有的新方法。
Tumor microenvironment (TME) stimuli-responsive nanoassemblies are emerging as promising drug delivery systems (DDSs), which acquire controlled release by structural transformation under exogenous stimulation. However, the design of smart stimuli-responsive nanoplatforms integrated with nanomaterials to achieve complete tumor ablation remains challenging. Therefore, it is of utmost importance to develop TME-based stimuli-responsive DDSs to enhance drug-targeted delivery and release at tumor sites. Herein, we proposed an appealing strategy to construct fluorescence-mediated TME stimulus-responsive nanoplatforms for synergistic cancer therapy by assembling photosensitizers (PSs) carbon dots (CDs), chemotherapeutic agent ursolic acid (UA), and copper ions (Cu2+). First, UA nanoparticles (UA NPs) were prepared by self-assembly of UA, then UA NPs were assembled with CDs via hydrogen bonding force to obtain UC NPs. After combining with Cu2+, the resulting particles (named UCCu2+NPs) exhibited quenched fluorescence and photosensitization due to the aggregation of UC NPs. Upon entering the tumor tissue, the photodynamic therapy (PDT) and the fluorescence function of UCCu2+were recovered in response to TME stimulation. The introduction of Cu2+triggered the charge reversal of UCCu2+NPs, thereby promoting lysosomal escape. Furthermore, Cu2+resulted in additional chemodynamic therapy (CDT) capacity by reacting with hydrogen peroxide (H2O2) as well as by consuming glutathione (GSH) in cancer cells through a redox reaction, hence magnifying intracellular oxidative stress and enhancing the therapeutic efficacy due to reactive oxygen species (ROS) therapy. In summary, UCCu2+NPs provided an unprecedented novel approach for improving the therapeutic efficacy through the three-pronged (chemotherapy, phototherapy, and heat-reinforced CDT) attacks to achieve synergistic therapy.