Light-Induced Liposomal Drug Delivery with an Amphiphilic Porphyrin and Its Chlorin and Bacteriochlorin Analogues.

The development of targeted drug delivery mechanisms in the human body is a matter of growing interest in medical science. The selective release of therapeutic agents at a specific target site can increase the therapeutical efficiency and at the same time reduce the side effects. Light-sensitive liposomes can release a drug by an externally controlled light trigger. Liposomes containing photosensitizers that can be activated in the longer wavelength range (650-800 nm) are particularly intriguing for medical purposes. This is because light penetration into a tissue is more efficient within this wavelength range, increasing their potential applications. For this study, liposomes with an encapsulated amphiphilic photosensitizer, the porphyrin 5,10-DiOH (5,10-di(4-hydroxyphenyl)-15,20-diphenyl-21,23H-porphyrin), its chlorin (5,10-DiOH-chlorin) and its bacteriochlorin (5,10-DiOH-bacteriochlorin) were synthesized. The porphyrin 5,10-DiOH showed previously effective cargo release after liposomal encapsulation when irradiated at a wavelength of 420 nm. The new synthesized chlorin and bacteriochlorin photosensitizers show additional absorption bands in the longer wavelength range, which would enable excitation in deeper layers of tissue. Effective cargo release with chlorin at a longer wavelength of 650 nm and bacteriochlorin at 740 nm was possible. Irradiation of chlorin allowed more than 75% of the cargo to be released and more than 60% for bacteriochlorin. The new liposomes would enable selective drug release in deeper tissue layers and expand the range of possible applications.

Optically Controlled Drug Release from Light-Sensitive Liposomes with the New Photosensitizer 5,10-DiOH.

The delivery of therapeutic drugs to a specific cellular site is a challenge in the treatment of different diseases. Liposomes have been widely studied as vehicles for drug delivery, and recent research begins to show the potential of the light-controlled opening of liposomes. Liposomes with photoactive molecules can release their cargo upon light irradiation for localized drug release. Light as an external trigger can be controlled temporally and spatially with high precision. In this study, we investigate the potential of light-sensitive liposomes with four photosensitizers and two lipid formulations for light-induced release. To investigate the permeabilization of the liposomes, calcein was encapsulated in high concentration inside the liposomes so that the calcein fluorescence is quenched. If calcein is released from the liposome, quenching is avoided, and the fluorescence increases. We demonstrated that liposomes with the sensitizers benzoporphyrine derivative monoacid (BPD), chlorine e6 (Ce6), Al(III) phthalocyanine chloride disulfonic acid (AlPcS2), and 5,10-di-(4-hydroxyphenyl)-15,20-diphenyl-21,23H-porphyrin (5,10-DiOH) release cargo effectively after irradiation. Liposomes with 5,10-DiOH showed a quicker release compared to the other sensitizers upon irradiation at 420 nm. Further, we observed through fractionated irradiation, that most of the release took place during light application, while the permeability of the liposome decreased shortly after light exposure. This effect was stronger with liposomes containing less cholesterol.

Photochemical Internalization with Fimaporfin: Enhanced Bleomycin Treatment for Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) still represents the world's sixth most common tumor entity, with increasing incidence. The reachability of light makes HNSCC suitable for light-based therapies such as Photochemical Internalization (PCI). The drug Bleomycin is cytotoxic and used as an anti-tumor medication. Since Bleomycin is endocytosed as a relatively large molecule, part of it is degraded in lysosomes before reaching its intracellular target. The goal of our study was to improve the intracellular availability of Bleomycin with PCI. We investigate the intracellular delivery of Bleomycin after PCI with the photosensitizer Fimaporfin. A systematic variation of Bleomycin and Fimaporfin concentrations and light irradiation led to the pronounced cell death of HNSCC cells. After optimization, the same level of tumor cell death of 75% was reached with a 20-fold lower Bleomycin concentration. This would allow treatment of HNSCC with high local tumor cell death and reduce the side effects of Bleomycin, e.g., lung fibrosis, at the same time. This demonstrates the increased efficacy of the anti-tumor medication Bleomycin in combination with PCI.