Photochemical internalization: a new tool for drug delivery.

The utilisation of macromolecules in the therapy of cancer and other diseases is becoming increasingly important. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. In many cases the targets of macromolecular therapeutics are intracellular.

Photochemical internalization (PCI): a new modality for light activation of endocytosed therapeuticals.

Photochemical internalization (PCI) is a new technology, where certain photosensitizing substances (photosensitizers) are used to improve the utilization of macromolecules for cancer therapy, in a site-specific manner. Degradation of macromolecules in endocytic vesicles after uptake by endocytosis is a major intracellular barrier for the therapeutic application of molecules having intracellular targets of action. PCI is based on the light activation of photosensitizers specifically located in the membrane of endocytic vesicles inducing the rupture of this membrane upon illumination.

Site-specific drug delivery by photochemical internalization enhances the antitumor effect of bleomycin.

Purpose: Photochemical internalization is under development for improving macromolecular therapy by inducing photochemical damage to endocytic vesicles. This damage leads to the release of therapeutic macromolecules entrapped in endocytic vesicles into the cytosol. The macromolecules may in this way be able to interact with therapeutic targets instead of being degraded by lysosomal hydrolases.

ALA-induced porphyrin formation and fluorescence in synovitis tissue In-vitro and in vivo studies.

The synovial inflammatory process in rheumatoid arthritis (RA) is accompanied by massive tumor-like proliferation and activation of the connective stroma. These abnormal cells actively invade and destroy the peri-articular bone and cartilage at the margins of joints where synovium and bone are attached. There is still a lack of minimally invasive synovectomy methods, which might be suitable for the smaller joints.

Transgene delivery and gelonin cytotoxicity enhanced by photochemical internalization in fibroblast-like synoviocytes (FLS) from rheumatoid arthritis patients.

The objective of this study was to determine if photochemical internalization (PCI) of gelonin can improve the treatment outcome as compared to photodynamic therapy (PDT) and gene transduction of fibroblast-like synoviocytes (FLS)in vitro. For this purpose synovial tissue was obtained under synovectomy of rheumatoid arthritis (RA) patients. Primary single cell suspensions were treated with the photosensitizer meso-tetraphenylporphine (TPPS2a) and light exposure (PDT) followed by evaluation of the cell survival by flow cytometry.