Nanoparticles of N-Vinylpyrrolidone Amphiphilic Copolymers and Pheophorbide a as Promising Photosensitizers for Photodynamic Therapy: Design, Properties and In Vitro Phototoxic Activity

Abstract

A series of nanoparticles (NPs) with a hydrodynamic radius from 20 to 100 nm in PBS was developed over the solubilization of hydrophobic dye methyl pheophorbide a (chlorin e6 derivative) by amphiphilic copolymers of N-vinylpyrrolidone with (di)methacrylates. Photophysical properties and biological activity of the NPs aqueous solution were studied. It was found that the dye encapsulated in the copolymers is in an aggregated state. However, its aggregation degree decreases sharply, and singlet oxygen quantum yield and the fluorescence signal increase upon the interaction of these NPs with model biological membranes—liposomes or components of a tissue homogenate. The phototoxic effect of NPs in HeLa cells exceeds by 1.5–2 times that of the reference dye chlorin e6 trisodium salt—one of the most effective photosensitizers used in clinical practice. It could be explained by the effective release of the hydrophobic photosensitizer from the NPs into biological structures. The demonstrated approach can be used not only for the encapsulation of hydrophobic photosensitizers for PDT but also for other drugs, and N-vinylpyrrolidone amphiphilic copolymers show promising potential as a modern platform for the design of targeted delivery vehicles.

Design and Investigation of New Water-Soluble Forms of α-Tocopherol with Antioxidant and Antiglycation Activity Using Amphiphilic Copolymers of N-Vinylpyrrolidone

“…The results obtained on the antioxidant activity of CPL1-TP and CPL2-TP are associated with the release of TP from polymer particles when added to the homogenate. In a previous paper [ 43 ], we have shown that incubating NPs loaded by methylpheophorbide a (MPP) as a hydrophobic photosensitizer with liposomes and tissue homogenate leads to a slow increase in the fluorescence of MPP. Most parts of MPP are sent from NPs to biological targets in tissue homogenate within the first 15 min of incubation and achieve a peak by one hour.…”

“…Our studies have shown that amphiphilic copolymers based on N -vinylpyrrolidone (VP) with branches in polymer chains proved to be promising as platforms for lipophilic compounds (zinc tetraphenylporphyrinate, iron nitrosyl complexes, fullerenes, methyl pheophorbide a, etc.) [ 39 , 40 , 41 , 42 , 43 ] with low cytotoxicity and ability to penetrate cells in vitro to deliver the active agent [ 39 , 44 ].…”

Emerging Applications of Chlorella sp. and Spirulina (Arthrospira) sp.

“…Nanoparticles of N-vinylpyrrolidone amphiphilic copolymers and Pha processed from Spirulina sp. were evaluated as promising PSs; when irradiated with red light (λ = 660 nm), the in vitro phototoxic effect of the nanoparticles in HeLa cells exceeded by 1.5–2 times that of the reference dye chlorin e6 trisodium salt—one of the most effective PSs used in clinical practice [ 141 ]. A PDT based on chlorin e6 (Ce6) from Spirulina platensis not only confirmed the suppression of a mouse melanoma on the mouse left flank, but also the induction of systemic effects in non-irradiated tumors on the right flank, where no Ce6-PDT was given, by triggering an immune response [ 142 ].…”