Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells
Suzanne Gascon,
Angéla Giraldo Solano,
Wiam El Kheir,
Hélène Therriault,
Pierre Berthelin,
Bettina Cattier,
Bernard Marcos,
Nick Virgilio,
Benoit Paquette,
Nathalie Faucheux,
Marc-Antoine Lauzon
Affiliations
Suzanne Gascon
Laboratory of Cell-Biomaterial Biohybrid Systems, Department of Chemical and Biotechnological Engineering, Faculty of Engineering, Université de Sherbrooke, 2500 boul universite, Sherbrooke, QC J1K 2R1, Canada
Angéla Giraldo Solano
Department of nuclear medicine and radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 12e avenue Nord, Sherbrooke, QC J1H 5N4, Canada
Wiam El Kheir
Advanced dynamic cell culture systems laboratory, Department of Chemical and Biotechnology Engineering, Faculty of Engineering, Université de Sherbrooke, 2500 boul universite, Sherbrooke, QC J1K 2R1, Canada
Hélène Therriault
Department of nuclear medicine and radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 12e avenue Nord, Sherbrooke, QC J1H 5N4, Canada
Pierre Berthelin
Laboratory of Cell-Biomaterial Biohybrid Systems, Department of Chemical and Biotechnological Engineering, Faculty of Engineering, Université de Sherbrooke, 2500 boul universite, Sherbrooke, QC J1K 2R1, Canada
Bettina Cattier
Advanced dynamic cell culture systems laboratory, Department of Chemical and Biotechnology Engineering, Faculty of Engineering, Université de Sherbrooke, 2500 boul universite, Sherbrooke, QC J1K 2R1, Canada
Bernard Marcos
Department of Chemical and Biotechnology Engineering, Faculty of Engineering, Université de Sherbrooke, 2500 boul universite, Sherbrooke, QC J1K 2R1, Canada
Nick Virgilio
Department of chemical engineering, Polytechnique Montréal, Montréal, QC H3C 3A7, Canada
Benoit Paquette
Department of nuclear medicine and radiobiology, Faculty of Medicine and Health Science, Université de Sherbrooke, 12e avenue Nord, Sherbrooke, QC J1H 5N4, Canada
Nathalie Faucheux
Laboratory of Cell-Biomaterial Biohybrid Systems, Department of Chemical and Biotechnological Engineering, Faculty of Engineering, Université de Sherbrooke, 2500 boul universite, Sherbrooke, QC J1K 2R1, Canada
Marc-Antoine Lauzon
Advanced dynamic cell culture systems laboratory, Department of Chemical and Biotechnology Engineering, Faculty of Engineering, Université de Sherbrooke, 2500 boul universite, Sherbrooke, QC J1K 2R1, Canada
Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, as a therapeutic approach, to control the migration of cancerous cells infiltrated in peri-tumoral tissues similar to those of glioblastoma multiforme (GBM). For this purpose, we prepared Alg/Chit NPs entrapping CXCL12 and characterized them. We demonstrated that Alg/Chit NPs, with an average size of ~250 nm, entrapped CXCL12 with ~98% efficiency for initial mass loadings varying from 0.372 to 1.490 µg/mg NPs. The release kinetic profiles of CXCL12 were dependent on the initial mass loading, and the released chemokine from NPs after seven days reached 12.6%, 32.3%, and 59.9% of cumulative release for initial contents of 0.372, 0.744, and 1.490 µg CXCL12/mg NPs, respectively. Mathematical modeling of released kinetics showed a predominant diffusive process with strong interactions between Alg and CXCL12. The CXCL12-NPs were not toxic and did not promote F98 GBM cell proliferation, while the released CXCL12 kept its chemotaxis effect. Thus, we developed an efficient and tunable CXCL12 delivery system as a promising therapeutic strategy that aims to be injected into a hydrogel used to fill the cavity after surgical tumor resection. This system will be used to attract infiltrated GBM cells prior to their elimination by conventional treatment without affecting a large zone of healthy brain tissue.