Polymer-porphyrin conjugates with application in photodynamic therapy

Alžběta Turnovská
Lecture of the lecture cycle
16.12.2024 11:00, Lecture room A

Photodynamic therapy uses a light-sensitive photosensitizer (PS), such as pyropheophorbide-a (PyFa) or tetraphenyl-porphyrin (TPP), in combination with illumination at appropriate wavelength for the treatment of cancer. The light-activated PS then reacts with oxygen, forming reactive oxygen species (i.e. singlet oxygen) and inducing cell death. The main drawbacks in the use of PS involves limited solubility in physiological conditions and hydrophobicity. To overcome these obstacles, water-soluble, and non-toxic polymer nanocarriers, such as N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, can be employed to carry PS and improve its physico-chemical properties. Moreover, due to the Enhanced Permeability and Retention (EPR) effect, the nanocarriers are passively accumulated in the tumour tissue amplifying the therapeutic outcome. Herein, we present the synthesis, and subsequent biological and physico-chemical evaluation of polymer-PS nanoconjugates. PS´s derivatives were bound in the nanoconjugates by hydrazone bonds with either aliphatic or aromatic spacer, or by stable amide bond. The structure-release rate dependency was studied in conditions mimicking the neutral blood conditions and acidic tumour environment. In vitro evaluation of cytotoxicity and intracellular uptake, as well as preliminary in vivo experiments were carried out. Fluorescence and CMC were measured to understand micelle formation and overall behaviour in physiological conditions.

The lecture is presented in English