Folate-Decorated Redox/Ph Dual-Responsive Degradable Prodrug Micelles for Tumor Triggered Targeted Drug Delivery Publisher



Tabatabaei Rezaei SJ¹ ; Sarbaz L¹ ; Niknejad H^{2, 3}
Source: RSC Advances Published:2016

Abstract

To address the obstacles facing the clinical use of paclitaxel, including poor water solubility, side effects and lack of tumor selectivity, a novel folate-decorated and redox and pH dual-responsive micellar drug delivery system was developed based on folate-poly(ethylene glycol)-b-poly((α-paclitaxel-SS-caprolactone)-co-caprolactone) (i.e., FA-PEG-b-P((PTX-SS-CL)-co-CL)) conjugates with thiol and acid-cleavable linkages. The paclitaxel (PTX) conjugated amphiphilic block copolymer prodrug was self-assembled in phosphate buffer (pH 7.4, 0.1 M) into nanosized spherical micelles (∼96.5 nm). In vitro release studies demonstrated that the prodrug micelles are relatively stable at normal physiologic conditions but susceptible to tumor-relevant reductive and acidic conditions which would trigger the release of chemically loaded drugs. Notably, folate-decorated PTX prodrug micelles based on FA-PEG-b-P((PTX-SS-CL)-co-CL) conjugates displayed apparent targetability to folate receptor-overexpressing HeLa cells. MTT assays showed that the therapeutic efficacy of these micelles against HeLa cancer cells (IC50 = 0.75 μg mL-1) was enhanced compared with free PTX (IC50 = 0.87 μg mL-1). These results suggest that FA-PEG-b-P((PTX-SS-CL)-co-CL) conjugates may offer a promising strategy for PTX delivery in the treatment of various tumors, with enhanced efficacy and fewer adverse effects. © 2016 The Royal Society of Chemistry.