Targeted phenylboronic acid-rosuvastatin based nanoconstructs: A novel therapeutic avenue for treatment of colorectal cancer.

Abstract

Inhibition of HMG-CoA reductase by rosuvastatin (RBX) hampers the synthesis of essential biosynthetic products required for cell proliferation, thereby exerting potent anti-cancer efficacy. However, low bioavailability, lack of targeting, and side effects limit clinical usage. Thus, to surpass these limitations and enable active targeting, RBX-loaded phenylboronic acid nanoconstructs (pPBA-RBX/NCs) were developed and optimized using central composite design (CCD) in Design-Expert® software. Nanoconstructs had an optimal size (182.4 ± 1.55), monodisperse nature (0.24 ± 0.05), maximum DL (39.12 ± 1.02%), and spherical shape. Due to the intrinsic property of the boronic ester, a pH-dependent sustained release was observed for 96 h. Tumor-targeting efficiency of the nanoconstructs was substantiated by cell culture studies in colon cancer cell lines, and efficacy testing in a preclinical model. Safety assessment of pPBA-RBX/NCs showed insignificant changes in the systemic biomarker levels and hemocompatibility. Overall, the developed pPBA nanoconstructs offer a novel framework for an effective and targeted delivery of therapeutics.