期刊
ACTA BIOMATERIALIA
卷 18, 期 -, 页码 132-143出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2015.02.022
关键词
Breast cancer; Metastasis; Targeted drug delivery; Chemotherapy; Cisplatin
资金
- National Natural Science Foundation of China [51173184, 51373168, 51390484, 51233004, 51321062]
- Ministry of Science and Technology of China [2011DFR51090]
- Program of Scientific Development of Jilin Province [20130727050YY, 20130206066GX]
The metastasis of breast cancer is the leading cause of cancer death in women. In this work, an attempt to simultaneously inhibit the primary tumor growth and organ-specific metastasis by the cisplatin-loaded LHRH-modified dextran nanoparticles (Dex-SA-CDDP-LHRH) was performed in the 4T1 orthotopic mammary tumor metastasis model. With the rationally designed conjugation site of the LHRH ligand, the Dex-SA-CDDP-LHRH nanoparticles maintained the targeting function of LHRH and specifically bound to the LHRH-receptors overexpressed on the surface of 4T1 breast cancer cells. Therefore, the Dex-SA-CDDP-LHRH nanoparticles exhibited improved cellular uptake and promoted cytotoxicity, when compared with the non-targeted Dex-SA-CDDP nanoparticles. Moreover, both the non-targeted and targeted nanoparticles significantly decreased the systemic toxicity of CDDP and increased the maximum tolerated dose of CDDP from 4 to 30 mg kg(-1). Importantly, Dex-SA-CDDP-LHRH markedly enhanced the accumulation of CDDP in the injected primary tumor and metastasis-containing organs, and meanwhile significantly reduced the nephrotoxicity of CDDP. Dose-dependent therapeutic effects further demonstrated that the CDDP-loaded LHRH-decorated polysaccharide nanoparticles significantly enhanced the antitumor and antimetastasis efficacy, as compared to the non-targeted nanoparticles. These results suggest that Dex-SA-CDDP-LHRH nanoparticles show great potential for targeted chemotherapy of metastatic breast cancer. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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