Overcoming ROS Resistance of Photodynamic Therapy with Self‐Assembled Nano‐Prodrugs for Efficient Triple‐Negative Breast Cancer
Overcoming ROS Resistance of Photodynamic Therapy with Self‐Assembled Nano‐Prodrugs for Efficient Triple‐Negative Breast Cancer
复制标题
DOI：
10.1002/adfm.202309524
复制
发表时间：
2023-10
影响因子：
19
通讯作者：
Bowen Li;Jianwu Tian;Xin Xie;Fu-You Zhang;Chongzhi Wu;Yi Shan;Guobin Qi;Wentao Song;
中科院分区：
文献类型：
--
作者：
Bowen Li;Jianwu Tian;Xin Xie;Fu-You Zhang;Chongzhi Wu;Yi Shan;Guobin Qi;Wentao Song;
三阴性乳腺癌（TNBC）具有高度侵袭性，导致远处转移和高复发率，但传统化疗的成功率有限。可激活的光敏剂（PS）可以提供一种有效和非侵入性的策略，通过提供刺激响应性活性氧（ROS）以精确的方式诱导TNBC细胞死亡。然而，ROS的毒性通常被TNBC细胞中ROS抗性的本能行为减轻甚至失活。为了解决这个问题，本文提出了一种小分子自组装纳米前药，以共同递送可活化的PS和ROS抗性抑制剂。在TNBC细胞中，过表达的谷胱甘肽可以分解纳米前药，从而释放ROS抗性抑制剂并激活PS用于光动力治疗和荧光成像。在皮下和原位TNBC小鼠模型上，进一步证明了混合膜包衣辅助的纳米颗粒形成策略可有效抑制肿瘤生长和远处转移。
Triple‐negative breast cancer (TNBC) is endowed with a highly aggressive nature that results in distant metastases and high recurrence rates, yet limited success is realized in traditional chemotherapy. Activatable photosensitizers (PSs) may provide an effective and non‐invasive strategy to induce TNBC cell death in a precise way by offering stimuli‐responsive reactive oxygen species (ROS). However, the toxicity of ROS is often mitigated and even devitalized by the instinctive behavior of ROS resistance in TNBC cells. To address this issue, herein a small molecular self‐assembly nano‐prodrug is presented to co‐deliver an activatable PS and ROS resistance inhibitor. In TNBC cells, the overexpressed glutathione can disassemble the nano‐prodrug, thereby releasing ROS resistance inhibitor and activating the PS for photodynamic therapy and fluorescence imaging. A hybrid membrane coating‐assisted nanoparticle formation strategy is further demonstrated for efficient inhibition of tumor growth and distant metastases on both subcutaneous and orthotopic TNBC mice models.