Polymeric Hybrid Nanomicelles for Cancer Theranostics: an Efficient and Precise Anticancer Strategy for the Co-delivery of Doxorubicin/miR-34a and MR imaging

To realize precise tumor therapy, a versatile oncotherapy nanoplatform integrating both diagnostic and therapeutic functions is necessary. Herein, we fabricated a hybrid micelle (HM) utilizing two amphiphilic diblock copolymers, polyethylenimine-polycaprolactone (PEI-PCL) and diethylenetriaminepentaacetic acid gadolinium(III)  (Gd-DTPA)-conjugated polyethyleneglycol-polycaprolactone (Gd-PEG-PCL), to codeliver the small-molecule chemotherapy drugs doxorubicin (Dox) and microRNA-34a (miR-34a), denoted as Gd-HM-Dox/34a. Conjugating Gd-DTPA on the surface of hybrid micelles, leading the relaxation rate of Gd-DTPA increased more than 1.4 times (13.6 mM–1 S–1). Furthermore, hybrid micelles enhanced the ability of miR-34a to escape from lysosomes/endosomes and Dox release to the nucleus. In addition, the released miR-34a subsequently downregulates Bcl-2, cyclin D1, CDK6, and Bax expression and inhibits proliferation and migration of MDA-MB-231 breast cancer cells. Moreover, the suitable micelle size improved the...