Gascon Suzanne, Giraldo Solano Angéla, El Kheir Wiam, Therriault Hélène, Berthelin Pierre, Cattier Bettina, Marcos Bernard, Virgilio Nick, Paquette Benoit, Faucheux Nathalie, Lauzon Marc-Antoine
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.
Department of nuclear medicine and radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 12e avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Pharmaceutics. 2020 Apr 14;12(4):356. doi: 10.3390/pharmaceutics12040356.
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.
目前用于制备脑用纳米颗粒（NPs）的壳聚糖（Chit）可与带负电荷的聚合物如海藻酸盐（Alg）复合，以更好地包裹带正电荷的分子如CXCL12。由递送系统产生的持续CXCL12梯度可作为一种治疗方法，用于控制浸润在肿瘤周围组织中的癌细胞迁移，类似于多形性胶质母细胞瘤（GBM）。为此，我们制备了包裹CXCL12的Alg/Chit NPs并对其进行了表征。我们证明，平均尺寸约为250 nm的Alg/Chit NPs对初始质量负载从0.372至1.490 μg/mg NPs的CXCL12的包裹效率约为98%。CXCL12的释放动力学曲线取决于初始质量负载，对于初始含量为0.372、0.744和1.490 μg CXCL12/mg NPs的情况，NPs释放的趋化因子在7天后分别达到累积释放量的12.6%、32.3%和59.9%。释放动力学的数学模型显示主要是扩散过程，Alg与CXCL12之间有强烈相互作用。CXCL12-NPs无毒且不促进F98 GBM细胞增殖，而释放的CXCL12保持其趋化作用。因此，我们开发了一种高效且可调的CXCL12递送系统，作为一种有前景的治疗策略，旨在注入用于在手术切除肿瘤后填充腔隙的水凝胶中。该系统将用于在通过传统治疗消除浸润的GBM细胞之前吸引它们，而不影响大片健康脑组织。
