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ACS nano:蔡林涛等开发联合化学-光热治疗新手段

来源:深圳先进技术研究院 2013-03-29 21:06

近日,中国科学院深圳先进技术研究院生物医药与技术研究所(筹)蔡林涛研究员带领的纳米医学研究小组,通过纳米体系共传递化疗药物和热疗试剂技术,并联合近红外激光照射使热疗试剂产生癌细胞敏感性的热,可以促使化疗药物更易发挥作用,攻克多药耐药,杀死癌细胞。研究成果在线发表在纳米领域期刊ACS nano上(2013,7 (3),2056–2067,影响因子:11.421)。这一成果或促进开发出治疗肿瘤的新手段。

联合化学-光热治疗被视为癌症治疗的新策略。为了确保化疗药物和光热试剂能够被同时传输到肿瘤部位发挥多重协同功能,开发安全高效的传输系统颇受青睐。蔡林涛组采用美国FDA批准的磷脂和聚合物为载体,以一步超声的方法制备出共包载化疗药物(阿霉素)和光热试剂(吲哚青绿)的脂-聚合物核壳纳米颗粒(DINPs)。研究结果表明纳米颗粒具备优良的荧光/粒径稳定性,在激光激发下产生比游离的吲哚青绿更高的温度响应,同时能有效延长化疗药物在肿瘤内的驻留时间。颗粒内的阿霉素及吲哚青绿的荧光能利用进行细胞及活体原位、实时、无损监控。

研究发现,与单一的化疗和热疗手段相比,单次瘤内注射DINPs加以激光照射的化学-光热联合治疗能够协同诱导药敏MCF-7乳腺癌细胞的凋亡和坏死;同时能够完全抑制荷MCF-7乳腺癌裸鼠的肿瘤生长。90天后未见肿瘤复发。这种复合“鸡尾酒”式疗法对于耐药的MCF-7/ADR乳腺肿瘤同样有效。

据悉,前期工作结果,包载吲哚青绿的脂-聚合物核壳肿瘤纳米探针在体内及体外成像发表在Biomaterials上(2012, 33 (22), 5603- 5609,影响因子:7.404),已受到国内外的广泛关注。(生物谷Bioon.com)

Single-Step Assembly of DOX/ICG Loaded Lipid–Polymer Nanoparticles for Highly Effective Chemo-photothermal Combination Therapy

Mingbin Zheng †‡, Caixia Yue †, Yifan Ma †, Ping Gong †, Pengfei Zhao †, Cuifang Zheng †, Zonghai Sheng †, Pengfei Zhang †, Zhaohui Wang †, and Lintao Cai †*

A combination of chemotherapy and photothermal therapy has emerged as a promising strategy for cancer therapy. To ensure the chemotherapeutic drug and photothermal agent could be simultaneously delivered to a tumor region to exert their synergistic effect, a safe and efficient delivery system is highly desirable. Herein, we fabricated doxorubicin (DOX) and indocyanine green (ICG) loaded poly(lactic-co-glycolic acid) (PLGA)–lecithin–polyethylene glycol (PEG) nanoparticles (DINPs) using a single-step sonication method. The DINPs exhibited good monodispersity, excellent fluorescence/size stability, and consistent spectra characteristics compared with free ICG or DOX. Moreover, the DINPs showed higher temperature response, faster DOX release under laser irradiation, and longer retention time in tumor. In the meantime, the fluorescence of DOX and ICG in DINPs was also visualized for the process of subcellular location in vitro and metabolic distribution in vivo. In comparison with chemo or photothermal treatment alone, the combined treatment of DINPs with laser irradiation synergistically induced the apoptosis and death of DOX-sensitive MCF-7 and DOX-resistant MCF-7/ADR cells, and suppressed MCF-7 and MCF-7/ADR tumor growth in vivo. Notably, no tumor recurrence was observed after only a single dose of DINPs with laser irradiation. Hence, the well-defined DINPs exhibited great potential in targeting cancer imaging and chemo-photothermal therapy.

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