State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.
Biomaterials. 2013 Apr;34(11):2719-30. doi: 10.1016/j.biomaterials.2012.12.040. Epub 2013 Jan 19.
The development of multidrug resistance (MDR) in cancer cells is one of major obstacles to the effective cancer chemotherapy. In this report we demonstrate the effective circumvention of multidrug resistance in cancer cells by an active nuclear-targeted drug delivery system that was constructed by conjugating TAT peptide onto the surface of mesoporous silica nanoparticles (MSNs-TAT). The conjugation of TAT peptide facilitated the intranuclear localization of MSNs-TAT and the release of the encapsulated drugs directly within the nucleoplasm. The direct intranuclear drug delivery of doxorubicin (DOX) in multidrug resistant MCF-7/ADR cancer cells was capable of increasing the intracellular as well as intranuclear drug concentrations much more effectively than free DOX or delivered by MSNs in the absence of TAT peptide. With the nuclear drug delivery fashion, DOX-MSNs-TAT presents a promising strategy in overcoming MDR in cancer cells and improving the therapeutic index of currently available chemotherapeutics by enhancing therapeutic efficacy and reducing side effects.
癌细胞多药耐药（MDR）的发展是癌症化疗有效治疗的主要障碍之一。在本报告中，我们通过将 TAT 肽缀合到介孔硅纳米粒子（MSNs-TAT）表面上构建的主动核靶向药物传递系统，证明了该系统可有效克服癌细胞的多药耐药性。TAT 肽的缀合促进了 MSNs-TAT 的核内定位和包封药物在核质内的直接释放。多药耐药 MCF-7/ADR 癌细胞中阿霉素（DOX）的直接核内药物传递能够比游离 DOX 或没有 TAT 肽的 MSNs 更有效地增加细胞内和核内药物浓度。通过核内药物传递方式，DOX-MSNs-TAT 通过增强治疗效果和减少副作用，为克服癌细胞多药耐药性和提高现有化疗药物的治疗指数提供了一种很有前途的策略。
