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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.