期刊
BIOMATERIALS
卷 51, 期 -, 页码 161-172出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.02.002
关键词
Cancer model; Colorectal carcinoma; Mammary carcinoma; Metastasis; Doxorubicin; Chemotherapy
资金
- National Natural Science Foundation of China [51173184, 51373168, 21104076, 51233004, 51390484, 51321062]
- Ministry of Science and Technology of China (International Cooperation and Communication Program) [2011DFR51090]
- Program of Scientific Development of Jilin Province [20130727050YY, 20130206066GX]
As a synergistic drug combination, doxorubicin-loaded cisplatin crosslinked polysaccharide-based nanoparticles (Dex-SA-DOX-CDDP) have demonstrated enhanced antitumor efficacy and reduced systemic toxicity via optimized biodistribution, controlled drug release, prolonged blood circulation, and improved tolerability, compared to the non-crosslinked nanoparticles or free doxorubicin. Herein, we apply the Dex-SA-DOX-CDDP nanoparticles as an efficient antitumor agent to treat colorectal and breast tumors in three different in vivo models, i.e. subcutaneously implanted colorectal carcinoma, dimethylhydrazine-induced autochthonous colorectal carcinoma, and metastatic mammary carcinoma, which more closely simulate the natural milieu of the original tumor with intact pathological and immunological responses. Based on the properties of this combination in higher tumor accumulation and penetrating efficiency, the Dex-SA-DOX-CDDP nanoparticles significantly decreased the tumor sizes in CT26 cell line xenograft tumors compared to control. In addition, the affected animals' lifespan was significantly extended after the Dex-SA-DOX-CDDP treatment, in the autochthonous colon cancer model. Moreover, with the aid of iRGD, Dex-SA-DOX-CDDP could effectively block primary tumor growth and prevent the metastasis of 4T1 murine mammary carcinoma. In conclusion, Dex-SA-DOX-CDDP nanoparticles remarkably inhibit growth of colorectal carcinoma and metastasis of mammary carcinoma in vivo, which provides potential application as a safe and efficient antitumor agent in treatment of these cancers. (C) 2015 Elsevier Ltd. All rights reserved.
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