Effective delivery of porphyrazine photosensitizers to cancer cells by polymer brush nanocontainers

Abstract

Efficient drug delivery can be assigned to tasks that attract the most acute attention of researchers in the field of anticancer drug design. We have reported the first case of using amphiphilic polymer brushes as nanocontainers for photosensitizer delivery to cancer cells. Regular graft-copolymers of hydrophobic polyimides with hydrophilic polymethacrylic acid side chains were loaded with photosensitive dye tetra(4-fluorophenyl)tetracyanoporphyrazine (Pz) providing a sufficiently stable homogeneous fraction of fluorescent Pz-loaded nanoparticles with a size of 100-150 nm. Pz-loaded polymer brushes were substantially more efficient for Pz delivery into cells compared with other types of particles examined, Pz-polyethyleneglycol and Pz-methylcellulose. In vivo, an efficient Pz delivery to tumor can also be expected since the Pz-PB particle size is in the optimal range for passive targeting. Pz-PB showed pronounced photodynamic activity, while, that is important, in the absence of irradiation the PB carrier itself was significantly less toxic than the dye itself. Summing up, water-soluble polymer brushes with polyimide backbones and polymethacrylic acid side chains can be regarded as a novel type of nanocontainers providing efficient intracellular drug delivery for photodynamic therapy of cancers.

Imaging tumor microscopic viscosity in vivo using molecular rotors

“…Additionally, we measured the viscosity of collagen in CT26 tumor in mice using BODIPY1 dissolved in polymeric brushes. Synthetic organic nanoparticles are a promising alternative to liposomes and polymersomes, which allow to achieve high reproducibility of a formulation properties via controlled synthesis and excellent encapsulation of hydrophobic dyes 52 . This encapsulation avoids excessive binding to albumins in the blood (as observed in the case of liposomes, due to a high affinity of our probes to albumin 33 ) and ensures the delivery of nanocarriers containing the rotor to tumours.…”

“…This encapsulation avoids excessive binding to albumins in the blood (as observed in the case of liposomes, due to a high affinity of our probes to albumin 33 ) and ensures the delivery of nanocarriers containing the rotor to tumours. Amphiphilic polymeric brushes used here are regular graft-copolymers of hydrophobic polyimide (PI) with hydrophilic polymethacrylic acid (PMAA) side chains forming particles that were about 100–150 nm in size 52 . The binding of BODIPY1 to polymeric brushes is due to hydrophobic interactions of the dye with PI and hydrogen bonding of the heterocyclic core with PMAA carboxyl groups.…”

“…We performed MTT assays of all probes at the working conditions used in this manuscript and we find no evidence of toxicity, Figure S7 . The viability of cultured cells exposed to polymeric brushes was previously evaluated in 52 and high cell viability was confirmed.…”

Cyano-Aryl Porphyrazine Pigments with Polycyclic Substituents as the Promising Agents for Photodynamic Therapy and Potential Sensors of Local Viscosity

“…It was found that potential therapeutic index (IC 50 (dark)/IC 50 (light)) of pzIV is much greater than that for another described cyano-aryl porphyrazines. [11][12][13]22] Additionally, this tetrapyrrol macrocycle as the most of cyano-aryl porphyrazines demonstrates photophysical behaviour of the fluorescent molecular rotor, i.e., high sensitivity of the fluorescence parameters to local viscosity. We believe that the combination of properties of highly efficient photosensitizer in PDT and the sensitive intracellular viscosity sensor enable significant enhancement of the pzIV functionality as a potential agent of optical theranostics.…”

Effect of novel porphyrazine photosensitizers on normal and tumor brain cells

“…Recently, several novel pz photosensitizers with cyano and aryl substituents in the periphery of the tetrapyrrole macrocycle have been described . The unique feature of the cyanoarylporphyrazines (hereafter referred to as pz ) is that their photophysical properties are highly sensitive to the viscosity of the medium.…”