Targeted delivery of cisplatin by LHRH-peptide conjugated dextran nanoparticles suppresses breast cancer growth and metastasis

Acta Biomaterialia
Mingqiang LiXuesi Chen

Abstract

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 30mgkg(-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 nanopar...Continue Reading

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Citations

Oct 11, 2015·Biotechnology Advances·Anuradha SubramanianSwaminathan Sethuraman
Mar 2, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wantong SongXuesi Chen
Apr 21, 2016·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Qinqin Cheng, Yangzhong Liu
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Jul 15, 2017·Expert Review of Anticancer Therapy·Aayushi JainNilesh Kumar Sharma
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Aug 1, 2019·Current Pharmaceutical Biotechnology·Hasanain Gomhor J AlqaraghuliRonak Rafipour
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Jun 21, 2020·Anti-cancer Agents in Medicinal Chemistry·Arezou Masteri FarahaniMostafa Erfani
May 1, 2021·International Journal of Molecular Sciences·Vrinda GoteDhananjay Pal

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