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

Jieni Xu, Jingjing Sun, Pui Yan Ho, Zhangyi Luo, Weina Ma, Wenchen Zhao, Sanjay B. Rathod, Christian A. Fernandez, Raman Venkataramanan, Wen Xie, Aiming Yu, Song Li

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)25-40
Number of pages16
JournalBiomaterials
Volume210
DOIs
StatePublished - Jul 1 2019

Keywords

  • Bioengineered miRNA prodrug
  • Cancer metastasis
  • Chemo-gene combination therapy
  • Creatine
  • Multifunctional nanocarriers

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Xu, J., Sun, J., Ho, P. Y., Luo, Z., Ma, W., Zhao, W., Rathod, S. B., Fernandez, C. A., Venkataramanan, R., Xie, W., Yu, A., & Li, S. (2019). Creatine based polymer for codelivery of bioengineered MicroRNA and chemodrugs against breast cancer lung metastasis. Biomaterials, 210, 25-40. https://doi.org/10.1016/j.biomaterials.2019.04.025