Review of Mechanisms of Photodynamic and Photothermal therapy by Water-Soluble Conjugate Polymers and Their Applications in Drug and Gene Delivery.

Abstract

Water-soluble conjugated polymers (WSCPs) represent an important class of functional macromolecules that combine the electronic advantages of π-conjugated polymer backbones with aqueous processability, biocompatibility, and tunable biointerfacial behavior. Unlike conventional small-molecule photosensitizers or inorganic nanomaterials, WSCPs offer polymeric design flexibility through controlled backbone engineering, side-chain functionalization, amphiphilicity, charge density, molecular weight, and nanoparticle self-assembly. These structural parameters govern their optical absorption, fluorescence emission, exciton migration, reactive oxygen species generation, photothermal conversion, colloidal stability, cellular uptake, and interactions with biomolecules. This review discusses the fundamental polymeric principles underlying WSCP performance, including π-electron delocalization, light-harvesting amplification, Förster resonance energy transfer, electrostatic complexation, hydrophobic association, and stimulus-responsive conformational changes. Particular emphasis is placed on how charged, PEGylated, glycosylated, and amphiphilic side chains improve water solubility, reduce nonspecific interactions, and enable targeted interactions with nucleic acids, proteins, membranes, and tumor cells. The review further summarizes the use of WSCPs and conjugated polymer nanoparticles in photodynamic therapy, photothermal therapy, antimicrobial treatment, drug delivery, and gene delivery. In photodynamic and photothermal applications, WSCPs act as light-responsive therapeutic platforms by generating singlet oxygen or other reactive oxygen species, converting absorbed light into localized heat, or combining both effects for synergistic therapy. In drug and gene delivery, their hydrophobic conjugated domains, cationic functionalities, and intrinsic fluorescence enable payload encapsulation, nucleic acid condensation, real-time tracking, and triggered release. Overall, WSCPs provide a versatile polymer-based platform for theranostic medicine, where molecular structure, photophysics, and biofunctionality can be rationally integrated to improve imaging, therapeutic efficacy, and targeted delivery.