Telodendrimer nanocarrier for co-delivery of paclitaxel and cisplatin: A synergistic combination nanotherapy for ovarian cancer treatment.

Telodendrimer nanocarrier for co-delivery of paclitaxel and cisplatin: A synergistic combination nanotherapy for ovarian cancer treatment.
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用于紫杉醇和顺铂共递送的Telodendrimer纳米载体:一种用于卵巢癌治疗的协同组合纳米疗法。

DOI:
10.1016/j.biomaterials.2014.10.044
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发表时间:
2015-01
期刊:
影响因子:
14
通讯作者:
Luo, Juntao
Luo, Juntao
中科院分区:
工程技术1区
文献类型:
--
作者:
Cai, Liqiong;Xu, Gaofei;Shi, Changying;Guo, Dandan;Wang, Xu;Luo, Juntao

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顺铂(CDDP)和紫杉醇(PTX)是两种已建立的化疗药物,用于联合治疗许多癌症,包括卵巢癌。我们最近开发了一种三层线性树枝状telodendrimer胶束(TM),通过引入羧酸基团在相邻层通过“硫烯”点击化学CDDP络合和共轭胆酸通过肽化学在telodendrimer的内层PTX封装。我们推测,低剂量PTX与CDDP的联合给药可以协同作用,以提高治疗效果并降低其毒副作用。这种设计使我们能够以各种药物比例向卵巢癌细胞共同递送PTX和CDDP。体外细胞测定显示,当以1:2的PTX/CDDP负载比递送时,抗肿瘤作用的协同作用最强。使用SKOV-3卵巢癌异种移植小鼠模型,我们证明,当与游离药物组合或单载TM制剂相比时,我们的共包封方法导致有效的肿瘤靶向药物递送、降低的细胞毒性作用和更强的抗肿瘤作用。
Cisplatin (CDDP) and paclitaxel (PTX) are two established chemotherapeutic drugs used in combination for the treatment of many cancers, including ovarian cancer. We have recently developed a three-layered linear-dendritic telodendrimer micelles (TM) by introducing carboxylic acid groups in the adjacent layer via “thio-ene” click chemistry for CDDP complexation and conjugating cholic acids via peptide chemistry in the interior layer of telodendrimer for PTX encapsulation. We hypothesize that the co-delivery of low dosage PTX with CDDP could act synergistically to increase the treatment efficacy and reduce their toxic side effects. This design allowed us to co-deliver PTX and CDDP at various drug ratios to ovarian cancer cells. The in vitro cellular assays revealed strongest synergism in anti-tumor effects when delivered at a 1:2 PTX/CDDP loading ratio. Using the SKOV-3 ovarian cancer xenograft mouse model, we demonstrate that our co-encapsulation approach resulted in an efficient tumor-targeted drug delivery, decreased cytotoxic effects and stronger anti-tumor effect, when compared with free drug combination or the single loading TM formulations.
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