Phenylboronic acid functionalized resveratrol-based nanomedicines with enhanced targeting for synergistic chemo-photothermal breast cancer therapy

Abstract

The combination of photothermal therapy (PTT) and chemotherapy (CT) offers a promising approach for enhanced cancer treatment. In this study, phenylboronic acid (PBA)-functionalized resveratrol (Res) oligomers were synthesized via Mannich condensation and used as therapeutic nanocarriers to co-deliver doxorubicin (Dox) and IR780, yielding two nanomedicines termed RsvDI and RevDI NPs. Both formulations exhibited good colloidal stability and effective drug loading, enabling simultaneous chemotherapy and photothermal therapy. RevDI NPs showed pH- and laser-responsive Dox release, supporting controlled drug delivery within the tumor microenvironment. In vitro studies confirmed that the Res-based carrier retained intrinsic anticancer activity while preserving the cytotoxic efficacy of Dox. Cellular uptake and in vivo/ex vivo fluorescence imaging demonstrated efficient tumor accumulation of both nanomedicines, with RevDI NPs achieving higher tumor targeting efficiency due to increased PBA density. In vivo antitumor studies revealed that RevDI NPs achieved a tumor inhibition rate of 87.5% under synergistic chemo-photothermal treatment, without inducing observable toxicity in major organs. Overall, this work highlights PBA-functionalized Res-based nanomedicines as an effective platform for targeted and synergistic cancer therapy, offering potential for further translational development.