Polydopamine-Coated Polyphenol-Based Nanoparticles for Synergistic Chemotherapy and Photothermal Therapy

Abstract

Enhanced permeability and retention (EPR) in cancerous cells and tissues provides an opportunity for designing nanomaterials-based drug delivery systems (NanoDDS) for anticancer applications. Chemotherapy (CT) and photothermal therapy (PTT)─two modes of treating cancers─can be employed synergistically by designing suitable NanoDDS to enhance their efficacy. Herein, we engineered an effective multilayered NanoDDS for combination cancer therapy by employing a suitably designed amino acid amphiphile, amenable to reaction by the enzyme horseradish peroxidase (HRP). Coating the precursor particles with polydopamine (PDA) imparted PTT capabilities to these nanoparticles (NPs), and entrapping doxorubicin (Dox) provided CT capabilities. An additional layering of spontaneously formed gold nanoparticles (AuNPs) on these NPs further augmented their PTT capabilities. The resulting PDA_Dox_Au@NPs achieved a solution temperature increase of > + 19 °C upon NIR illumination at 1 W/cm2 for 4 minutes, with a photothermal conversion efficiency of 14%. Moreover, the NIR illumination unraveled these NPs and released the Dox entrapped within, resulting 44% cumulative Dox release. These NPs were efficiently internalized into cancer cells and induced strong anticancer effects. This work highlights the utility of enzyme reactions in engineering multilayered NanoDDS for potential synergistic anticancer therapy. © 2026 American Chemical Society