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Creatine based polymer for codelivery of bioengineered MicroRNA and chemodrugs against breast cancer lung metastasis
- 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
- Biomaterials 2019 v.210 pp. 25-40
- breast neoplasms, composite polymers, creatine, doxorubicin, drug therapy, gene expression regulation, immune response, metastasis, microRNA, mortality
- 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.