Multifunctional Nanosystem for Targeted and Controlled Delivery of Multiple Chemotherapeutic Agents for the Treatment of Drug-Resistant Breast Cancer.
Multifunctional Nanosystem for Targeted and Controlled Delivery of Multiple Chemotherapeutic Agents for the Treatment of Drug-Resistant Breast Cancer.
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DOI：
10.1021/acsomega.8b00949
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发表时间：
2018-08-31
期刊：
影响因子：
4.1
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Lou S;Zhao Z;Dezort M;Lohneis T;Zhang C
通过靶向CD 44受体，抑制多药耐药性（MDR），控制药物释放，协同抑制肿瘤生长，开发了一种多层纳米系统，作为治疗耐药乳腺癌的多功能平台。多层纳米系统由聚（乳酸-共-乙醇酸）核心、脂质体第二层和壳聚糖第三层组成。壳聚糖-多层纳米颗粒（Ch-MLNPs）可以共递送三种化疗剂：多柔比星（DOX）、紫杉醇（PTX）和水飞蓟宾。这三种药物在细胞内体中内化和定位后以受控和顺序的方式从多层NP中释放。壳聚糖层的存在使纳米系统能够靶向一种充分表征的MDR乳腺癌生物标志物，即CD 44 s受体。体外细胞毒性实验表明，阿霉素-紫杉醇-水飞蓟宾三药纳米系统的抗肿瘤效果优于单药或双药纳米制剂。可能归因于水飞蓟宾的MDR抑制作用，共同递送的DOX和PTX对MDR乳腺癌细胞比对非MDR乳腺癌细胞表现出更好的协同作用。体内研究还表明，多层纳米系统促进了MDR抑制和化疗剂之间的协同作用，导致异种移植动物模型中的肿瘤显著减少。与对照组相比，Ch-MLNP使肿瘤体积减小了五倍，而没有引起明显的细胞毒性。
By targeting CD44 receptors, inhibiting multidrug resistance (MDR), controlling drug release, and synergistically inhibiting tumor growth, a multilayered nanosystem was developed to serve as a multifunctional platform for the treatment of drug-resistant breast cancers. The multilayer nanosystem is composed of a poly(lactic-co-glycolic acid) core, a liposome second layer, and a chitosan third layer. The chitosan-multilayered nanoparticles (Ch-MLNPs) can co-deliver three chemotherapeutic agents: doxorubicin (DOX), paclitaxel (PTX), and silybin. The three drugs are released from the multilayered NPs in a controlled and sequential manner upon internalization and localization in the cellular endosomes. The presence of a chitosan layer allows the nanosystem to target a well-characterized MDR breast cancer biomarker, the CD44s receptor. In vitro cytotoxicity study showed that the nanosystem loaded with triple drugs, DOX–PTX–silybin, resulted in better antitumor efficacy than the single-drug or dual-drug nano-formulations. Likely attributed to the MDR-inhibition effect of silybin, the co-delivered DOX and PTX exhibited a better synergistic effect on MDR breast cancer cells than on non-MDR breast cancer cells. The in vivo study also showed that the multilayered nanosystem promoted MDR inhibition and synergy between chemotherapeutic agents, leading to significant tumor reduction in a xenograft animal model. Ch-MLNPs reduced the tumor volume by fivefold compared to that of the control group without causing overt cytotoxicity.
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影响因子：
13.3
作者：
Chen, Alex M.;Zhang, Min;Wei, Dongguang;Stueber, Dirk;Taratula, Oleh;Minko, Tamara;He, Huixin
通讯作者：
He, Huixin
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影响因子：
17.1
作者：
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通讯作者：
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影响因子：
14
作者：
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通讯作者：
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影响因子：
9.7
作者：
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通讯作者：
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影响因子：
10.3
作者：
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通讯作者：
Schinkel, AH