Drug-Loaded Photosensitizer-Chitosan Nanoparticles for Combinatorial Chemo- and Photodynamic-Therapy of Cancer

• Published in: Biomacromolecules
• Main Authors: Pandya, Abhilash D., Øverbye, Anders, Sahariah, Priyanka, Gaware, Vivek S., Høgset, Håkon, Másson, Már, Høgset, Anders, Mælandsmo, Gunhild M., Skotland, Tore, Sandvig, Kirsten, Iversen, Tore-Geir
• Other Authors: Lyfjafræðideild (HÍ), Faculty of Pharmaceutical Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Chemical Society (ACS) 2020
• Subjects: Biodegradable polymers; Mertansine; Cabazitaxel; Breast cancer cells; Lyfjaefnafræði; Fjölliður; Brjóstakrabbamein; Norway; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/2378; https://doi.org/10.1021/acs.biomac.0c00061

Publisher's version (útgefin grein) In this study we have developed biodegradable polymeric nanoparticles (NPs) containing the cytostatic drugs mertansine (MRT) or cabazitaxel (CBZ). The NPs are based on chitosan (CS) conjugate polymers synthesized with different amounts of the photosensitizer tetraphenylchlorin (TPC). These TPC-CS NPs have high loading capacity and strong drug retention due to π-πstacking interactions between the drugs and the aromatic photosensitizer groups of the polymers. CS polymers with 10% of the side chains containing TPC were found to be optimal in terms of drug loading capacity and NP stability. The TPC-CS NPs loaded with MRT or CBZ displayed higher cytotoxicity than the free form of these drugs in the breast cancer cell lines MDA-MB-231 and MDA-MB-468. Furthermore, light-induced photochemical activation of the NPs elicited a strong photodynamic therapy effect on these breast cancer cells. Biodistribution studies in mice showed that most of the TPC-CS NPs accumulated in liver and lungs, but they were also found to be localized in tumors derived from HCT-116 cells. These data suggest that the drug-loaded TPC-CS NPs have a potential in combinatory anticancer therapy and as contrast agents. This work was supported by The Research Council of Norway [NANO2021; Project Number 228200/O70] and The Norwegian Cancer Society. We thank Anne Engen for excellent assistance with cell culturing and Monika Håkerud for professional assistance regarding illumination of cells. We would also like to thank The Norwegian Radium Hospital Research Foundation (RADFORSK) for financial support and The Simon Fougner Hartmann Family Fund for providing means to analytical instrumentation. We also acknowledge a contribution from the University of Iceland Research Fund for the work in Iceland. Peer Reviewed