Highly efficient drug delivery systems based on functional supramolecular polymers: In vitro evaluation
Highly efficient drug delivery systems based on functional supramolecular polymers: In vitro evaluation
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DOI：
10.1016/j.actbio.2016.01.018
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发表时间：
2016-03-15
影响因子：
9.7
通讯作者：
Lee, Duu-Jong
中科院分区：
文献类型：
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作者：
Cheng, Chih-Chia;Chang, Feng-Chih;Lee, Duu-Jong
通过自互补相互作用修饰和增强现有功能胶束的性质的新概念具有显着的潜力。在这项研究中，一个实用的方法，功能化的温敏单体的活性聚合，使自我构成的多个氢键基团纳入胶束，具有潜在的超分子药物输送系统。在水溶液中的相变和形态学研究表明，可以控制的微观结构，以实现良好定义的囊泡状胶束相对于氢键段的强度。因此，所得胶束具有非常低的临界胶束化浓度和非常高的负载容量（16.1%），使得负载过程非常稳定和有效。抗癌药物阿霉素（DOX）的掺入影响了水溶液中的胶束化过程，并使药物负载的微调和药物释放速率的精确控制具有优异的灵敏度。体外释药研究表明，在37 ℃的生理温度下，载药胶束对人肝癌细胞（HepG2）具有剂量依赖性的细胞毒性。此外，载DOX的胶束被癌细胞有效地内吞，这可能使胶束能够用作将抗癌药物有效递送至原发性肿瘤和转移性疾病的合适载体。这一新开发的材料可能提供一个潜在的路线走向下一代药物输送vehicles.Statement of SignificanceA突破性创新的水基热响应聚合物已经使开发智能刺激响应纳米载体的重大进展，通过产生新的“超分子聚合物胶束”通过自互补氢键相互作用。这些新开发的胶束表现出极高的胶束稳定性和载药量（高达16%），优异的热响应行为和精确控制的药物释放速率，由于氢键诱导的物理交联。此外，装载阿霉素的胶束被癌细胞有效地内吞，这使得它们能够充当用于将抗癌药物有效递送至原发性肿瘤和转移性疾病的合适载体。因此，这项工作为开发下一代多功能纳米载体提供了一条潜在的途径，这些纳米载体具有更高的安全性，并提高了抗癌治疗的疗效。(C)2016 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The novel concept of modifying and enhancing the properties of existing functional micelles through self-complementary interactions has significant potential. In this study, a practical approach to living polymerization of functionalized thermoresponsive monomers enabled the incorporation of self constituted multiple hydrogen bonded groups into micelles that have potential as supramolecular drug-delivery systems. Phase transitions and morphological studies in aqueous solution showed that the microstructure can be controlled to achieve well-defined vesicle-like micelles with respect to the strength of the hydrogen bond segment. Thus, the resulting micelles have a very low critical micellization concentration and very high loading capacity (16.1%), making the loading process extremely stable and efficient. Incorporation of the anticancer drug doxorubicin (DOX) affected the micellization process in aqueous solution and enabled fine-tuning of drug loading and precise control of drug release rate with excellent sensitivity. Release studies in vitro showed that DOX-loaded micelles exerted dose dependent cytotoxicity against human liver carcinoma (HepG2) cells at the physiological temperature of 37 degrees C. In addition, DOX-loaded micelles were efficiently endocytosed by the cancer cells, which may enable the micelles to serve as suitable vehicles for effective delivery of anticancer drugs to primary tumors and metastatic disease. This newly developed material may provide a potential route towards next-generation drug delivery vehicles.Statement of SignificanceA breakthrough innovation in water-based thermo-responsive polymers has enabled significant progress in developing smart stimuli-responsive nanocarriers by generating novel "supramolecular polymeric micelles" via self-complementary hydrogen-bonding interactions. These newly developed micelles exhibit extremely high micellar stability and drug loading capacity (up to 16%), excellent thermo-responsive behavior and precise control of drug release rate due to hydrogen-bond-induced physical cross-linking. In addition, doxorubicin-loaded micelles were efficiently endocytosed by the cancer cells, which allows them to serve as suitable vehicles for effective delivery of anticancer drugs to primary tumors and metastatic disease. Thus, this work provides a potential route for the development of next generation multifunctional nanocarriers that have improved safety and to increase the therapeutic efficacy of anticancer therapy. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.