The Role of Polymer Encapsulation in Optimizing Donor–Acceptor Organic Nanoparticles for Efficient Cancer Phototherapy

Donor–acceptor (D–A) molecular systems are gaining increasing attention in cancer imaging and phototherapy due to their tunable optical properties and high photosensitizing efficiency. Encapsulation of such D–A molecules in nano-sized polymeric carriers can enhance the efficiency of antitumor therapy by passive tumor accumulation and controlled drug release. Here, we synthesized two D–A molecules—TTDCV and TTInd—based on triphenylamine with thiophene π-spacers and electron-withdrawing dicyanovinyl or indene-1,3-dione moieties. These molecules were used to preparate nanoparticles (NPs) via nanoprecipitation with amphiphilic polymers—poly(ethylene glycol)-block polylactide methyl ether (PEG-b-PLA) and polyethylene oxide-polypropylene oxide (PEO-PPO-PEO, Pluronic® F-127). The resulting NPs had spherical morphology, core–shell structure and a tunable mean size (66–139 nm), depending on the polymer type used. Photothermal and photodynamic properties of the NPs were confirmed by intracellular reactive oxygen species generation and efficient heating even under 530 nm low dose irradiation (1 J/cm2), leading to substantial in vitro cytotoxicity against Sk-Br-3 and MCF-7 human breast cancer cells. Pluronic-encapsulated systems showed the strongest effect, reducing IC50 values down to 0.99 µg/mL and achieving phototoxicity indices up to 22, accompanied by increased intracellular accumulation studied by confocal microscopy and flow cytometry. This study establishes relationships between molecular design, encapsulation approaches, and the biological performance of nanoparticles, enabling the rational engineering of D–A-derived nanotherapeutics for precision cancer treatment.