Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Acta Biomater. 2018 Jul 15;75:371-385. doi: 10.1016/j.actbio.2018.05.026. Epub 2018 May 17.
The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy.
The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.
化疗和光热疗法在多功能纳米囊泡中的结合已成为提高癌症治疗效果的一种有前途的策略。在此，我们设计了新的 pH/还原双重响应和叶酸修饰的聚合物胶束（FA Co-PMs）作为治疗诊断纳米载体，以共包封阿霉素（DOX）和吲哚菁绿（ICG）用于靶向近红外成像和化疗-光热联合治疗。Co-PMs 表现出纳米尺寸的结构（约 100nm），具有良好的单分散性，对 ICG 和 DOX 的包封效率高，对酸性 pH 和还原环境有触发 DOX 释放的作用，并且具有出色的温度转换能力，可进行激光照射。体外细胞摄取研究表明，FA Co-PMs 通过叶酸受体介导的内吞作用对 BEL-7404 细胞具有显著的靶向作用，激光诱导的热疗进一步增强了药物在癌细胞中的积累。体内生物分布研究表明，FA Co-PMs 通过 EPR 效应和 FA 靶向作用延长了药物循环并增强了药物在肿瘤中的积累。此外，基于 ICG 的光触发热疗与基于 DOX 的化疗协同诱导 BEL-7404 细胞死亡和凋亡，并有效抑制 BEL-7404 异种移植肿瘤的生长，同时显著降低体内系统毒性。因此，设计的双重响应 Co-PMs 是一种很有前途的多功能抗肿瘤药物递送和成像引导的癌症化疗-光热联合治疗的治疗诊断纳米载体。
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