Zhang Tianfu, Ping Wei, Suo Meng, Pan You, Huang Rong, Chen Jingqi, Lyu Meng, Zhang Ni, Ning Shipeng, Tang Ben Zhong
Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, School of Biomedical Engineering, Guangzhou Medical University, Guangdong 511436, China.
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan, Hubei 430030, China.
ACS Nano. 2024 Jul 24. doi: 10.1021/acsnano.4c04067.
The self-renewal and differentiation properties of cancer stem cells (CSCs) result in chemoresistance in breast cancer. Even though numerous drugs have been developed to target CSCs, they have suffered from inefficient delivery and accumulation at the focal site. Here, a thermoresponsive hydrogel is developed by coencapsulating aggregation-induced emission (AIE)-active photothermal agent and thioridazine (THZ), demonstrating a controllable delivery system triggered by the AIE agent to augment THZ-mediated CSC ablation. Upon near-infrared laser stimuli, the photothermal effect from the AIE agent induces hydrogel deformation for burst drug release. The precise tumor administration of the hydrogel accelerates drug diffusion and accumulation in deep breast cancer lesions. Thus, THZ can invade tumors and provoke massive CSC apoptosis via dopamine receptor blockage and oxidative stress induction. Consequently, effective CSC inhibition and significant suppression of tumor recurrence and metastasis are demonstrated in mice with breast cancer. We believe that this intelligent hydrogel-based delivery system represents a promising treatment strategy for metastatic breast cancer with clinical potential.
癌症干细胞（CSCs）的自我更新和分化特性导致乳腺癌产生化学抗性。尽管已经开发了许多针对CSCs的药物，但它们在病灶部位的递送和积累效率低下。在此，通过共包封聚集诱导发光（AIE）活性光热剂和硫利达嗪（THZ）开发了一种热响应水凝胶，展示了一种由AIE剂触发的可控递送系统，以增强THZ介导的CSC消融。在近红外激光刺激下，AIE剂产生的光热效应诱导水凝胶变形以实现药物的突释。水凝胶的精确肿瘤给药加速了药物在深部乳腺癌病灶中的扩散和积累。因此，THZ可通过阻断多巴胺受体和诱导氧化应激侵入肿瘤并引发大量CSC凋亡。结果，在患有乳腺癌的小鼠中证明了有效的CSC抑制以及对肿瘤复发和转移的显著抑制。我们相信，这种基于智能水凝胶 的递送系统代表了一种具有临床潜力的转移性乳腺癌的有前景的治疗策略。
