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Self‐Stabilized Hyaluronate Nanogel for Intracellular Codelivery of Doxorubicin and Cisplatin to Osteosarcoma
Advanced Science ( IF 14.3 ) Pub Date : 2018-02-15 , DOI: 10.1002/advs.201700821 Yi Zhang 1, 2 , Feng Wang 1 , Mingqiang Li 2 , Zhiqiang Yu 3 , Ruogu Qi 4 , Jianxun Ding 2 , Zhiyu Zhang 1 , Xuesi Chen 2
Advanced Science ( IF 14.3 ) Pub Date : 2018-02-15 , DOI: 10.1002/advs.201700821 Yi Zhang 1, 2 , Feng Wang 1 , Mingqiang Li 2 , Zhiqiang Yu 3 , Ruogu Qi 4 , Jianxun Ding 2 , Zhiyu Zhang 1 , Xuesi Chen 2
Affiliation
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Osteosarcoma is one of the most serious bone malignancies with rapid speed of deterioration and low survival rate in children and teenagers. Chemotherapy is an important treatment for osteosarcoma, while the conventional small‐molecule therapeutics exhibit low efficacies and severe side effects in the clinic. Drug‐delivery platforms based on nanotechnology, particularly for self‐stabilized delivery platforms with prolonged blood circulation, enhanced intratumoral accumulation, improved antitumor efficacy, and diminished side effects, may break the deadlock on osteosarcoma chemotherapy. Here, a cisplatin (CDDP)‐crosslinked hyaluronic acid (HA) nanogel (CDDPHANG) is prepared for effective delivery of doxorubicin (DOX) to treat osteosarcoma. Importantly, both DOX and CDDP have led clinically used antitumor drugs, and CDDP acts as a crosslinker and ancillary anticarcinogen to prevent the premature release of DOX and to achieve synergistic therapeutic performance. Because of the enhanced stability of the nanogel, this CDDP‐crosslinked DOX‐loaded nanomedicine (CDDPHANG/DOX) exhibits an obviously prolonged circulation time compared to free drugs. Moreover, after valid tumor accumulation, DOX and CDDP are synergistically delivered into the tumor cells and synchronously released into the intracellular acidic environment. Based on the synergistic apoptosis‐inducing effects of DOX and CDDP, CDDPHANG/DOX reveals an evidently enhanced antitumor efficacy compared to free drugs and their combination, indicating its great prospects for the chemotherapy of osteosarcoma.
中文翻译：
自稳定透明质酸纳米凝胶用于细胞内联合递送阿霉素和顺铂治疗骨肉瘤
骨肉瘤是最严重的骨恶性肿瘤之一，在儿童和青少年中恶化速度快，存活率低。化疗是骨肉瘤的重要治疗方法，而传统的小分子治疗在临床上疗效低且副作用严重。基于纳米技术的药物递送平台，特别是具有延长血液循环、增强瘤内蓄积、提高抗肿瘤疗效和减少副作用的自稳定递送平台，可能会打破骨肉瘤化疗的僵局。在此，制备了顺铂（CDDP）交联透明质酸（HA）纳米凝胶（CDDP HANG），用于有效递送阿霉素（DOX）来治疗骨肉瘤。重要的是，DOX和CDDP都引领了临床使用的抗肿瘤药物，CDDP作为交联剂和辅助抗癌剂，防止DOX过早释放，实现协同治疗性能。由于纳米凝胶的稳定性增强，这种CDDP交联的DOX负载纳米药物（CDDP HANG/DOX）与游离药物相比表现出明显延长的循环时间。此外，在肿瘤有效积累后，DOX和CDDP协同递送至肿瘤细胞内并同步释放至细胞内酸性环境中。基于DOX和CDDP的协同细胞凋亡诱导作用，CDDP HANG/DOX较游离药物及其组合显示出明显增强的抗肿瘤功效，表明其在骨肉瘤化疗方面的巨大前景。
更新日期：2018-02-15
中文翻译：
自稳定透明质酸纳米凝胶用于细胞内联合递送阿霉素和顺铂治疗骨肉瘤
骨肉瘤是最严重的骨恶性肿瘤之一，在儿童和青少年中恶化速度快，存活率低。化疗是骨肉瘤的重要治疗方法，而传统的小分子治疗在临床上疗效低且副作用严重。基于纳米技术的药物递送平台，特别是具有延长血液循环、增强瘤内蓄积、提高抗肿瘤疗效和减少副作用的自稳定递送平台，可能会打破骨肉瘤化疗的僵局。在此，制备了顺铂（CDDP）交联透明质酸（HA）纳米凝胶（CDDP HANG），用于有效递送阿霉素（DOX）来治疗骨肉瘤。重要的是，DOX和CDDP都引领了临床使用的抗肿瘤药物，CDDP作为交联剂和辅助抗癌剂，防止DOX过早释放，实现协同治疗性能。由于纳米凝胶的稳定性增强，这种CDDP交联的DOX负载纳米药物（CDDP HANG/DOX）与游离药物相比表现出明显延长的循环时间。此外，在肿瘤有效积累后，DOX和CDDP协同递送至肿瘤细胞内并同步释放至细胞内酸性环境中。基于DOX和CDDP的协同细胞凋亡诱导作用，CDDP HANG/DOX较游离药物及其组合显示出明显增强的抗肿瘤功效，表明其在骨肉瘤化疗方面的巨大前景。
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