Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu 610031, Sichuan, PR China.
ACS Nano. 2015 Feb 24;9(2):1161-74. doi: 10.1021/nn504573u. Epub 2015 Jan 23.
Nanocarriers have attracted broad attention in cancer therapy because of their ability to carry drugs preferentially into cancer tissue, but their application is still limited due to the systemic toxicity and low delivery efficacy of intravenously delivered chemotherapeutics. In this study, we develop a localized drug delivery device with combination of an active-targeting micellar system and implantable polymeric nanofibers. This device is achieved first by the formation of hydrophobic doxorubicin (Dox)-encapsulated active-targeting micelles assembled from a folate-conjugated PCL-PEG copolymer. Then, fabrication of the core-shell polymeric nanofibers is achieved with coaxial electrospinning in which the core region consists of a mixture of poly(vinyl alcohol) and the micelles and the outer shell layer consists of cross-linked gelatin. In contrast to the systematic administration of therapeutics via repeatedly intravenous injections of micelles, this implantable device has these capacities of greatly reducing the drug dose, the frequency of administration and side effect of chemotherapeutic agents while maintaining highly therapeutic efficacy against artificial solid tumors. This micelle-based nanofiber device can be developed toward the next generation of nanomedicine for efficient and safe cancer therapy.
纳米载体因其能够优先将药物输送到癌症组织而在癌症治疗中引起了广泛关注,但由于静脉内递送的化疗药物的全身毒性和低递送效率,其应用仍然受到限制。在这项研究中,我们开发了一种局部药物递送装置,将主动靶向胶束系统与可植入聚合物纳米纤维相结合。该装置首先通过形成疏水性阿霉素(Dox)包封的主动靶向胶束来实现,这些胶束由叶酸偶联的 PCL-PEG 共聚物组装而成。然后,通过同轴电纺丝制备核壳聚合物纳米纤维,其中核区域由聚(乙烯醇)和胶束的混合物组成,外壳层由交联明胶组成。与通过反复静脉内注射胶束进行系统治疗相比,这种可植入装置具有大大降低药物剂量、给药频率和化疗药物副作用的能力,同时保持对人工实体瘤的高度治疗效果。这种基于胶束的纳米纤维装置可以开发为下一代用于高效和安全癌症治疗的纳米医学。