Polymeric material based on cystamine-protoporphyrin IX connection in PLGA of potential utility in photodynamic therapy - preparation, physicochemical properties, and biological activity

By the use of suitable delivery systems and pharmaceutical formulations, improved transportation of photosensitizers to cancer cells in photodynamic therapy can be achieved. The aim of our study was to demonstrate controlled, redox-triggered release of a photosensitizer by developing a redox- and photo-responsive polymeric carrier system based on poly(lactic-co-glycolic acid) functionalized with cystamine and protoporphyrin IX, which could serve as a model for potential use in photodynamic therapy. During the study, polymeric materials based on cystamine-protoporphyrin IX combination incorporated in poly(lactic-co-glycolic acid) were obtained, characterised in physicochemical studies and subjected to biological assessment. The presence of cystamine enabled the PPIX release in the presence of thiol triggers. The physicochemical characterisation of the new material was performed using UV-Vis, IR, NMR spectroscopies, X-Ray diffraction, and thermogravimetric analysis. The size and morphology of the obtained material were determined using nanoparticle tracking analysis, as well as SEM and TEM microscopy. The photochemical properties and stability of the material were analysed by establishing the singlet oxygen generation and photodecomposition quantum yields. The acute toxicity of modified polymeric material was determined using the Microtox® test, whereas cyto- and photocytotoxicities were assessed in vitro on the human prostate cancer cell line (LNCaP) and human lung fibroblast (MRC-5). The polymer components, cystamine and PLGA, did not affect cell viability on their own, neither upon irradiation nor in the absence of light. The obtained polymeric material based on a protoporphyrin IX-cystamine molar ratio of 1:1 in PLGA could be considered a prospective formulation for PDT. The novelty of our study lies in the design of a dual-responsive (redox and light) PLGA-based carrier system encapsulating protoporphyrin IX and a redox-cleavable linker, enabling controlled, photo-triggered release of the photosensitizer.