基于肌酸的聚合物用于共递送生物工程化的 MicroRNA 和化疗药物治疗乳腺癌肺转移。
Creatine based polymer for codelivery of bioengineered MicroRNA and chemodrugs against breast cancer lung metastasis.
机构信息
Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Biochemistry and Molecular Medicine, School of Medicine, University of California-Davis, Sacramento, CA 96817, USA.
出版信息
Biomaterials. 2019 Jul;210:25-40. doi: 10.1016/j.biomaterials.2019.04.025. Epub 2019 Apr 26.
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.
转移是导致乳腺癌相关死亡的主要原因。基于 miRNA 的治疗与化疗相结合代表了一种有前途的治疗乳腺癌肺转移的方法。本研究的目的是开发一种改进的治疗方法，通过多功能纳米胶束载体共同递送新型生物工程 miRNA 前药（tRNA-mir-34a）和阿霉素（DOX），该载体基于亲水性嵌段共聚物 POEG-VBC 与肌氨酸的缀合物，肌氨酸是一种天然的阳离子分子。DOX 的共递送导致 tRNA-mir-34a 更有效地加工成成熟的 miR-34a，并下调靶基因。DOX + tRNA-mir-34a/POEG-PCre 在体外和体内均表现出强大的协同抗肿瘤和抗转移活性。有趣的是，增强的免疫反应有助于整体抗肿瘤疗效。POEG-PCre 可能代表了一种安全有效的递药系统，用于最佳的化疗-基因联合治疗。
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