Smart Polydopamine Nanodots-Knotted Hydrogels for Photodynamic Tumor Therapy

Abstract

Integrating nature-derived polyphenolic nanodots (PDs) with polymeric matrices presents a sustainable strategy for developing multifunctional nanocomposite hydrogels with enhanced biological performance. However, conventional PDs-knotted hydrogel fabrication methods still face significant challenges in regulating PDs properties and seamlessly incorporating them into hydrogel systems. Herein, we reported a facile and eco-friendly approach to construct polydopamine (PDA) nanodots via polyethyleneimine (PEI)-mediated oxidative polymerization under the mild aqueous conditions, avoiding harsh reagents and energy-intensive processes. These resulting PDs could further be simultaneously loaded with tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer to prepare empowered nanodots (PD & TCPP), which then served as the core building elements towards the fabrication of smart hydrogels with multiple stimulus-responsive properties via iminoboronate chemistry. The as-prepared hydrogels exhibited excellent water stability and promising responsiveness to tumor microenvironment stimuli, facilitating the precise and controlled release of PD & TCPPfor photodynamic therapy (PDT). In vitro and in vivo studies further confirmed the highly efficient PDT performance of the hydrogels for tumor treatment. This work presents a versatile strategy for engineering nanocomposite hydrogels with unique properties for biomedical applications.