**Thermoresponsive Zinc TetraPhenylPorphyrin Photosensitizer/Dextran Graft Poly(N-IsoPropylAcrylAmide) Copolymer/Au Nanoparticles Hybrid Nanosystem: Potential for Photodynamic Therapy Applications**

**Oleg A. Yeshchenko 1,\*, Nataliya V. Kutsevol 2,3, Anastasiya V. Tomchuk 1, Pavlo S. Khort 1, Pavlo A. Virych 2, Vasyl A. Chumachenko 2, Yulia I. Kuziv 2,3, Andrey I. Marinin 4, Lili Cheng 5 and Guochao Nie 5,\***


**Abstract:** The thermoresponsive Zinc TetraPhenylPorphyrin photosensitizer/Dextran poly (Nisopropylacrylamide) graft copolymer/Au Nanoparticles (ZnTPP/D-g-PNIPAM/AuNPs) triple hybrid nanosystem was synthesized in aqueous solution as a nanodrug for potential use in thermally driven and controlled photodynamic therapy applications. The aqueous solution of the nanosystem has demonstrated excellent stability in terms of aggregation and sedimentation several days after preparation. Optimal concentrations of the components of hybrid nanosystem providing the lowest level of aggregation and the highest plasmonic enhancement of electronic processes in the photosensitizer molecules have been determined. It has been revealed that the shrinking of D-g-PNIPAM macromolecule during a thermally induced phase transition leads to the release of both ZnTPP molecules and Au NPs from the ZnTPP/D-g-PNIPAM/AuNPs macromolecule and the strengthening of plasmonic enhancement of the electronic processes in ZnTPP molecules bound with the polymer macromolecule. The 2.7-fold enhancement of singlet oxygen photogeneration under resonant with surface plasmon resonance has been observed for ZnTPP/D-g-PNIPAM/AuNPs proving the plasmon nature of such effect. The data obtained in vitro on wild strains of *Staphylococcus aureus* have proved the high potential of such nanosystem for rapid photodynamic inactivation of microorganisms particular in wounds or ulcers on the body surface.

**Keywords:** thermoresponsive polymer; gold nanoparticles; photosensitizer; hybrid nanosystem; plasmon enhancement; singlet oxygen photogeneration; photodynamic therapy
