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载多柔比星羧甲基纤维素纳米粒联合恩度治疗非小细胞肺癌的协同抗肿瘤作用。

Synergistic antitumor effects of doxorubicin-loaded carboxymethyl cellulose nanoparticle in combination with endostar for effective treatment of non-small-cell lung cancer.

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China; University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.

出版信息

Adv Healthc Mater. 2014 Nov;3(11):1877-88. doi: 10.1002/adhm.201400108. Epub 2014 May 20.

DOI:10.1002/adhm.201400108
PMID:24846434
Abstract

The multi-modal combination therapy is proved powerful and successful to enhance the antitumor efficacy in clinics as compared with single therapy modes. In this study, the potential of combining chemotherapy with antiangiogenic therapy for the treatment of non-small-cell lung cancer is explored. Towards this aim, OEGylated carboxymethyl cellulose-(2-(2-(2-methoxyethoxy)ethoxy)methyl)oxirane (CMC-ME2MO) is prepared by treating CMC with ME2MO in the alkaline aqueous solution, and used to efficiently carry doxorubicin (DOX) with high drug-loading content (16.64%) and encapsulation efficiency (99.78%). As compared to free DOX, the resulting nanoparticles show not only the favorable stability in vitro but also the prolonged blood circulation, improved safety and tolerability, optimized biodistribution, reduced systemic toxicity, and enhanced antitumor efficacy in vivo, indicates a potential utility in cancer chemotherapy. Furthermore, the combination of the DOX-loaded polysaccharide nanoparticles and antiangiogenic drug endostar provides synergistic effects of chemotherapy and antiangiogenic therapy, which shows the highest efficiency in tumor suppression. The combination approach of the DOX-containing nanomedicine and endostar for efficient treatment of non-small-cell lung cancer is first proposed to demonstrate the synergistic therapeutic effect. This synergistic combination proves to be a promising therapeutic regimen in cancer therapy and holds great potential for clinical application.

摘要

多模态联合治疗在临床中被证明比单一治疗模式更能增强抗肿瘤疗效。在这项研究中,探索了将化疗与抗血管生成治疗联合用于治疗非小细胞肺癌的潜力。为此,通过在碱性水溶液中用 ME2MO 处理 CMC 来制备 OEG 化羧甲基纤维素-(2-(2-(2-甲氧基乙氧基)乙氧基)甲基)环氧乙烷(CMC-ME2MO),并用于高效携带具有高载药量(16.64%)和包封效率(99.78%)的阿霉素(DOX)。与游离 DOX 相比,所得纳米粒不仅具有体外良好的稳定性,而且具有延长的血液循环、改善的安全性和耐受性、优化的生物分布、降低的全身毒性以及增强的体内抗肿瘤疗效,表明其在癌症化疗中有潜在的应用价值。此外,载 DOX 的多糖纳米粒与抗血管生成药物恩度的联合使用提供了化疗和抗血管生成治疗的协同作用,在肿瘤抑制方面显示出最高的效率。首次提出了载 DOX 的纳米药物与恩度联合用于高效治疗非小细胞肺癌的联合方法,以证明协同治疗效果。这种协同联合被证明是癌症治疗中有前途的治疗方案,具有很大的临床应用潜力。

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