Comparative photophysical characterization of chitosan-coated isotropic and anisotropic gold nanoparticles conjugated with a phthalocyanine photosensitizer

Abstract

Multidrug resistance in pathogenic bacteria remains one of the most serious challenges facing modern medicine, driving the search for fundamentally new strategies that would prevent the emergence of resistance. A promising approach is combined photodynamic (PDT) and photothermal (PTT) therapy using conjugates of gold nanoparticles (AuNPs) with photosensitizers that are activated within the “phototherapeutic window” of 600–850 nm. This strategy significantly improves the bioavailability and stability of the photosensitizers. However, a key barrier to the use of gold nanorods is the presence of the cationic surfactant cetyltrimethylammonium bromide (CTAB), which is not only cytotoxic but also prevents further surface functionalization.
The aim of this study was to functionalize isotropic and anisotropic AuNPs with chitosan, conjugate them with the phthalocyanine photosensitizer “Photosens”, and comprehensively evaluate the photophysical properties of the resulting systems—including reactive oxygen species (ROS) generation, photothermal effect, and fluorescence emission—under red laser irradiation.
The ligand exchange process was performed stepwise, with careful monitoring at each stage. For spherical AuNPs, citrate ions were exchanged for a mixture of thiolated polyethylene glycol (mPEG) and 11 mercaptoundecanoic acid, whereas for gold nanorods (exhibiting a localized surface plasmon resonance at 670 nm), CTAB was replaced by carboxylated PEG SH. Chitosan was then covalently attached to the modified surface via EDC/NHS activation of the carboxyl groups. The success of each modification step was verified by ATR FTIR spectroscopy and dynamic light scattering (DLS).
The resulting chitosan coated AuNPs were then conjugated with “Photosens”. The final conjugates exhibited high colloidal stability, maintaining resistance to aggregation in phosphate buffered saline (pH 7.4) for up to 48 hours. Irradiation experiments at 200 mW/cm², which included thermographic measurements and the ABDA assay, revealed that the conjugates significantly outperformed the free photosensitizer in several respects: they showed synergistic enhancement of the photodynamic and photothermal effects, improved photostability, and a more sustained therapeutic action.
Taken together, these findings indicate that the developed chitosan functionalized AuNPs loaded with “Photosens” offer new prospects for combating antibiotic resistance.

Speaker

Puzanov-Tyurin D.A.
Institute of Biochemistry and Physiology of Plants and Microorganisms Russian Academy of Sciences (IBPPM RAS)
Russia

Discussion

Ask question