Triazine–Carbosilane Dendrimersomes Enhance Cellular Uptake and Phototoxic Activity of Rose Bengal in Basal Cell Skin Carcinoma Cells

Krzysztof Sztandera,1 Michał Gorzkiewicz,1,2 Mateusz Bątal,1 Valeria Arkhipova,3,4 Nadezhda Knauer,3,5,6 Javier Sánchez-Nieves,7,8 Fco Javier de la Mata,7– 9 Rafael Gómez,7– 9 Evgeny Apartsin,3,4,10 Barbara Klajnert-Maculewicz1 1Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, 90-236, Poland; 2Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany; 3Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, 630090, Russia; 4Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russia; 5Research Institute of Fundamental and Clinical Immunology, Novosibirsk, 630099, Russia; 6Clinic for Neurosurgery, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany; 7Departamento de Química Orgánica y Química Inorgánica, UAH-IQAR, Alcalá de Henares, 28805, Spain; 8Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, 28029, Spain; 9Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS, Madrid, 28034, Spain; 10Laboratoire de Chimie de Coordination CNRS, Toulouse, 31077, FranceCorrespondence: Barbara Klajnert-Maculewicz, Department of General Biophysics, Pomorska 141/143, Łódź, 90-236, Poland, Tel +48 42 635 44 29, Fax +48 42 635 4474, Email barbara.klajnert@biol.uni.lodz.plBackground: The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of photosensitizer, thereby avoiding side effects. The incorporation of photosensitizers into nanoassemblies is a versatile way to increase the efficiency and specificity of drug delivery into target cells. Herein, we report the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem.Methods: Using established protocol and analytical and spectroscopy techniques we were able to synthesized dendrons with strictly designed properties. Engaging biophysical methods (hydrodynamic diameter and zeta potential measurements, analysis of spectral properties, transmission electron microscopy) we confirmed assembling of our nanosystem. A set of in vitro techniques was used for determination ROS generation, (ABDA and H2DCFDA probes), cell viability (MTT assay) and cellular uptake (flow cytometry and confocal microscopy).Results: Encapsulation of rose bengal inside dendrimersomes enhances cellular uptake, intracellular ROS production and concequently, the phototoxicity of this photosensitizer.Conclusion: Triazine-carbosilane dendrimersomes show high capacity as drug carriers for anticancer photodynamic therapy.Graphical Abstract: Keywords: dendrons, amphiphiles, carbosilane, photodynamic therapy, rose bengal, dendrimersomes