Role of Polymer Micelles in the Delivery of Photodynamic Therapy Agent to Liposomes and Cells

Abstract

The use of nanocarriers for hydrophobic photosensitizers, in the context of photodynamic therapy (PDT) to improve pharmacokinetics and bio-distribution, is well-established. However, the mechanisms at play in the internalization of nanocarriers are not well-elucidated, despite its importance in nanocarrier design. In this study, we focus on the mechanisms involved in copolymer poly(ethylene oxide)-block-poly(ε-caprolactone) PEO-PCL and poly(ethylene oxide)-block-poly styrene PEO-PS micelles - membrane interactions through complementary physico-chemical studies on biomimetic membranes, and biological experiments on two-dimensional (2D) and three-dimensional (3D) cell cultures. Förster Resonance Energy Transfer measurements on fluorescently-labelled lipid vesicles, and flow cytometry on two cancerous cell lines enabled the evaluation in the uptake of a photosensitizer, Pheophorbide a (Pheo), and copolymer chains towards model membranes, and cells, respectively. The effects of calibrated light illumination for PDT treatment on lipid vesicle membranes, i.e., leakage and formation of oxidized lipids, and cell viability, were assessed. No significant differences were observed between the ability of PEO-PCL and PEO-PS micelles in delivering Pheo to model membranes, but Pheo was found in higher concentrations in cells in the case of PEO-PCL. These higher Pheo concentrations did not correspond to better performances in PDT treatment. We demonstrated that there are subtle differences in PEO-PCL and PEO-PS micelles for the delivery of Pheo.

Antimicrobial Photodynamic Therapy: Latest Developments with a Focus on Combinatory Strategies

“…Due to their structures, micelles are implicitly used to encapsulate hydrophobic drugs or agents, such as PSs, to convey the latter to the target (e.g., cancer cells or microbial infections) while overcoming their low solubility in aqueous media [374]. Additionally, encapsulation may reduce the toxicity of the PSs [375,376]. When compared with polymersomes, one disadvantage is the lack of flexibility to encapsulate or transport both hydrophilic and hydrophobic molecules.…”

Multifunctional Photoactive Nanomaterials for Photodynamic Therapy against Tumor: Recent Advancements and Perspectives

“…They enhance aqueous solubility and retain photo–sensitizer in the blood for a longer period, allowing its accumulation at the desired site –enhanced permeability and retention. However, these photosensitizers loaded polymeric micelles can cause skin photosensitivity, damaging the blood vessel cells or the endothelial cells [ 127 ]. Lamch et al fabricated folic acid conjugated polymeric micelles containing phthalocyanine for anticancer photodynamic therapy.…”

Non-Oncologic Applications of Nanomedicine-Based Phototherapy

“…A nanocarrier is a nanomaterial with 1–100 nm to deliver substances such as photosensitizers. The intrinsic characteristics of PSs with low water solubility and aggregating tendency lowers the therapeutic efficacy of phototherapy [ 55 ]. In order to improve the delivery of PSs, various kinds of nanocarriers have been developed.…”