Wei Tuo, Chen Chao, Liu Juan, Liu Cheng, Posocco Paola, Liu Xiaoxuan, Cheng Qiang, Huo Shuaidong, Liang Zicai, Fermeglia Maurizio, Pricl Sabrina, Liang Xing-Jie, Rocchi Palma, Peng Ling
Chinese Academy of Sciences Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, 100190 Beijing, People's Republic of China; Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, 13288 Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM U1068, F-13009 Marseille, France; Institut Paoli-Calmettes, F-13009 Marseille, France; Aix-Marseille Université, F-13284 Marseille, France; CNRS UMR7258, F-13009 Marseille, France; University of Chinese Academy of Sciences, 100049 Beijing, People's Republic of China;
Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, 13288 Marseille, France; Aix-Marseille Université, CNRS, Institut de Chimie Radicalaire, UMR 7273, 13390 Marseille, France;
Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):2978-83. doi: 10.1073/pnas.1418494112. Epub 2015 Feb 23.
Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy.
耐药性和毒性是癌症治疗面临的具有挑战性的障碍。纳米技术在抗癌药物递送中的应用有望解决这些问题,并为癌症治疗带来新的希望。在此背景下,我们基于两亲性树枝状聚合物(AmDM)建立了一种原创的纳米胶束药物递送系统,该系统能够产生超分子胶束,由于独特的树枝状结构为药物容纳创造了大的空隙空间,从而能够以高载药量(>40%)有效包封抗癌药物阿霉素(DOX)。所得的AmDM/DOX纳米胶束能够通过显著增强细胞摄取同时大幅减少药物外排来增强药物效力并对抗乳腺癌模型中的阿霉素耐药性。此外,AmDM/DOX纳米颗粒显著消除了与游离药物相关的毒性。总体而言,我们的研究表明,基于由自组装两亲性树枝状聚合物形成的纳米胶束的药物递送系统在癌症治疗中构成了一种有前景且有效的药物载体。