Folic acid-targeted polymeric complex imprinted with doxorubicin and quercetin for controlled drug delivery in cancer therapy

Abstract

Cancer therapy is often limited by the systemic toxicity and dose-dependent adverse effects of conventional chemotherapeutic agents such as doxorubicin (DOX). In this study, a folic acid-functionalized molecularly imprinted polymeric complex based on poly(HEMA) crosslinked with ethylene glycol dimethacrylate was synthesized for the controlled release of DOX in combination with quercetin (QUE), a flavonoid known for its antioxidant and chemosensitizing properties. The aim of this work was to develop and physicochemically characterize a preliminary targeted drug delivery platform at a material-design level. The polymeric complex was synthesized via free-radical polymerization following a DOX–QUE precomplex formation step. Structural characterization was performed using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) analyses. SEM micrographs revealed nanoscale spherical and partially aggregated polymeric domains, while FTIR spectra confirmed the successful incorporation of DOX, QUE, and folic acid into the poly(HEMA) matrix. In vitro release studies were conducted in 0.1 M acetate buffer at pH 5.5 to simulate mildly acidic tumor-relevant conditions. Within 180 min, measurable release was observed, with 0.0011 mg of DOX and 0.0978 mg of QUE released from the system. Thus, this study demonstrates the structural feasibility of a folic acid-functionalized imprinted polymer system capable of controlled release under acidic conditions, presenting a material-level physicochemical evaluation of a dual-drug imprinted polymeric platform. Biological validation, including cytotoxicity assays and receptor-mediated uptake studies, is not addressed in this study and remains necessary for comprehensive therapeutic assessment.