Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
Department of Pharmacy, Saarland University, Saarbrücken, Germany; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Center for Infection Research (HZI) Department of Drug Delivery (DDEL), Saarbrücken, Germany.
Nanomedicine. 2019 Oct;21:102073. doi: 10.1016/j.nano.2019.102073. Epub 2019 Jul 31.
Biodegradable polymeric nanoparticles (NP) made from poly (lactid-co-glycolide) acid (PLGA) and chitosan (CS) hold promise as innovative formulations for targeted delivery. Since interactions of such NP with primary human immune cells have not been characterized, yet, here we assessed the effect of PLGA or CS-PLGA NP treatment on human peripheral blood mononuclear cells (PBMC), as well as on monocyte-derived DC (moDC). Amongst PBMC, antigen presenting cells (APC) showed higher uptake of both NP preparations than lymphocytes. Furthermore, moDC internalized CS-PLGA NP more efficiently than PLGA NP, presumably because of receptor-mediated endocytosis. Consequently, CS-PLGA NP were delivered mostly to endosomal compartments, whereas PLGA NP primarily ended up in lysosomes. Thus, CS-PLGA NP confer enhanced delivery to endosomal compartments of APC, offering new therapeutic options to either induce or modulate APC function and to inhibit pathogens that preferentially infect APC.
可生物降解的聚合物纳米粒子(NP)由聚(乳酸-共- 乙醇酸)酸(PLGA)和壳聚糖(CS)制成,有望成为靶向递药的创新制剂。由于尚未对这种 NP 与原代人免疫细胞的相互作用进行表征,因此在这里,我们评估了 PLGA 或 CS-PLGA NP 处理对人外周血单核细胞(PBMC)以及单核细胞衍生的树突状细胞(moDC)的影响。在 PBMC 中,抗原呈递细胞(APC)比淋巴细胞摄取更多的两种 NP 制剂。此外,moDC 比 PLGA NP 更有效地内化 CS-PLGA NP,这可能是因为受体介导的内吞作用。因此,CS-PLGA NP 主要递送至 APC 的内体区室,而 PLGA NP 主要递送至溶酶体。因此,CS-PLGA NP 增强了 APC 内体区室的递药,为诱导或调节 APC 功能以及抑制优先感染 APC 的病原体提供了新的治疗选择。