Overcoming Chemoresistance in Cancer via Combined MicroRNA Therapeutics with Anticancer Drugs Using Multifunctional Magnetic Core-Shell Nanoparticles

Perry T. Yin, Thanapat Pongkulapa, Hyeon Yeol Cho, Jiyou Han, Nicholas J. Pasquale, Hudifah Rabie, Jong-Hoon Kim, Jeong Woo Choi, Ki Bum Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

In this study, we report the use of a multifunctional magnetic core-shell nanoparticle (MCNP), composed of a highly magnetic zinc-doped iron oxide (ZnFe2O4) core nanoparticle and a biocompatible mesoporous silica (mSi) shell, for the simultaneous delivery of let-7a microRNA (miRNA) and anticancer drugs (e.g., doxorubicin) to overcome chemoresistance in breast cancer. Owing to the ability of let-7a to repress DNA repair mechanisms (e.g., BRCA1 and BRCA2) and downregulate drug efflux pumps (e.g., ABCG2), delivery of let-7a could sensitize chemoresistant breast cancer cells (MDA-MB-231) to subsequent doxorubicin chemotherapy both in vitro and in vivo. Moreover, the multifunctionality of our MCNPs allows for the monitoring of in vivo delivery via magnetic resonance imaging. In short, we have developed a multifunctional MCNP-based therapeutic approach to provide an attractive method with which to enhance our ability not only to deliver combined miRNA therapeutics with small-molecule drugs in both selective and effective manner but also to sensitize cancer cells for the enhanced treatment via the combination of miRNA replacement therapy using a single nanoplatform.

Original languageEnglish
Pages (from-to)26954-26963
Number of pages10
JournalACS Applied Materials and Interfaces
Volume10
Issue number32
DOIs
Publication statusPublished - 2018 Aug 15

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Keywords

  • chemoresistance
  • combination cancer therapy
  • magnetic core-shell nanoparticles
  • microRNA therapeutics
  • targeted delivery

ASJC Scopus subject areas

  • Materials Science(all)

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