Octa-Cationic Porphyrin-Functionalized Biocompatible Nanocomposite: A Promising Candidate for Enhanced Combinatorial Photodynamic and Photothermal Tumor Therapy

The integration of photodynamic therapy (PDT) and photothermal therapy (PTT) offers a promising strategy for enhancing phototherapy efficiency. Herein, we present a dual-functional, biocompatible nanocomposite system for combination PDT/PTT therapy. The system utilizes a highly biocompatible nanoparticle assembled by an amphiphilic short peptide with the assistance of Zn²⁺ as a carrier. The photothermal convertor is loaded within the nanoparticle, while a cationic porphyrin photosensitizer is assembled on the surface. The water-soluble cationic porphyrin (M₈PzEOPP), designed with eight positive charges, provides a strong electrostatic interaction for stable assembly on the nanocomposite surface. This location-independent assembly effectively maintains the optical characteristics of both the photosensitizer and the photothermal convertor, endowing the nanocomposite with effective photodynamic and photothermal properties. The nanocomposite exhibits excellent tumor-targeting accumulation behavior, low dark toxicity, robust extracellular biostability, and high cell internalization efficiency. Its enhanced performance in combinatorial therapy is demonstrated through both in vitro and in vivo experiments.