Chitosan-based Carriers for Photochemical Internalisation in Cancer Therapy
Photochemical internalisation (PCI) is the application of a photosensitiser (PS) molecule and light to direct and aid the intracellular localisation of proteins and other macromolecular drugs.
PCI has shown promise to enhance the efficacy of various macromolecular cancer drugs that cannot penetrate into cancer cells under normal conditions. PCI Biotech AS is developing PCI for clinical application. The first phase I clinical trial (PCI of bleomycin) has recently been approved in Norway.
The aim of the current project is to develop nano-carriers for photosensitisers, which will be based on chitosan biopolymers, and will have optimal properties for uptake and photochemically activated delivery of macromolecular drugs.
The purpose of the carrier, apart from increasing the solubility, is to improve specificity of the uptake of PSs. Due to large size of the carrier enhanced permeation and retention (EPR) in tumors can be expected. The polymeric carriers should stimulate cellular uptake of the PSs and should therefore improve delivery relative to currently used PSs.
The uptake of chitosan carriers into cancer cell will be studied by confocal microscopy. Confocal microscopy and standard cytotoxicity assays will be used to study light-induced release of macromolecular drugs into cytosol of cancer cells in order to select the most potent carriers. In vivo evaluation of the chitosan carriers will be performed on mouse models carrying human tumor xenografts to validate biodistribution and therapeutic potential of chitosan carriers.