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Creatine based polymer for codelivery of bioengineered MicroRNA and chemodrugs against breast cancer lung metastasis.

  • Author(s): Xu, Jieni
  • Sun, Jingjing
  • Ho, Pui Yan
  • Luo, Zhangyi
  • Ma, Weina
  • Zhao, Wenchen
  • Rathod, Sanjay B
  • Fernandez, Christian A
  • Venkataramanan, Raman
  • Xie, Wen
  • Yu, Ai-Ming
  • Li, Song
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pubmed/31054369
No data is associated with this publication.
Abstract

Metastasis is the major cause for breast cancer related mortality. The combination of miRNA-based therapy and chemotherapy represents a promising approach against breast cancer lung metastasis. The goal of this study is to develop an improved therapy that co-delivers a novel bioengineered miRNA prodrug (tRNA-mir-34a) and doxorubicin (DOX) via a multifunctional nanomicellar carrier that is based on a conjugate of amphiphilic copolymer POEG-VBC backbone with creatine, a naturally occurring cationic molecule. Co-delivery of DOX leads to more effective processing of tRNA-mir-34a into mature miR-34a and down-regulation of target genes. DOX + tRNA-mir-34a/POEG-PCre exhibits potent synergistic anti-tumor and anti-metastasis activity in vitro and in vivo. Interestingly, the enhanced immune response contributes to the overall antitumor efficacy. POEG-PCre may represent a safe and effective delivery system for an optimal chemo-gene combination therapy.

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