Targeted delivery of cisplatin by LHRH-peptide conjugated dextran nanoparticles suppresses breast cancer growth and metastasis
Targeted delivery of cisplatin by LHRH-peptide conjugated dextran nanoparticles suppresses breast cancer growth and metastasis
复制标题
LHRH-肽缀合的葡聚糖纳米颗粒靶向递送顺铂可抑制乳腺癌生长和转移
DOI：
10.1016/j.actbio.2015.02.022
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发表时间：
2015-05-01
影响因子：
9.7
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
--
作者：
Li, Mingqiang;Tang, Zhaohui;Chen, Xuesi
乳腺癌的转移是女性癌症死亡的主要原因。本研究在4T1原位乳腺肿瘤转移模型中，通过顺铂负载lhrh修饰的葡聚糖纳米颗粒（Dex-SA-CDDP-LHRH）同时抑制原发肿瘤生长和器官特异性转移。通过合理设计LHRH配体的偶联位点，Dex-SA-CDDP-LHRH纳米颗粒保持了LHRH的靶向功能，并特异性结合4T1乳腺癌细胞表面过表达的LHRH受体。因此，与非靶向的Dex-SA-CDDP纳米颗粒相比，Dex-SA-CDDP- lhrh纳米颗粒表现出更好的细胞摄取和增强的细胞毒性。此外，非靶向和靶向纳米颗粒均显著降低了CDDP的全身毒性，并将CDDP的最大耐受剂量从4 mg kg增加到30 mg kg（-1）。重要的是，Dex-SA-CDDP-LHRH显著增强了注射后原发肿瘤和含转移器官中CDDP的积累，同时显著降低了CDDP的肾毒性。剂量依赖性的治疗效果进一步表明，与非靶向纳米粒子相比，负载cdp的lhrh修饰多糖纳米粒子显著增强了抗肿瘤和抗转移的功效。这些结果表明，Dex-SA-CDDP-LHRH纳米颗粒在转移性乳腺癌的靶向化疗中具有很大的潜力。(C) 2015材料学报Elsevier Ltd.出版。版权所有。
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.