Fontana Flavia, Lindstedt Hanna, Correia Alexandra, Chiaro Jacopo, Kari Otto K, Ndika Joseph, Alenius Harri, Buck Jonas, Sieber Sandro, Mäkilä Ermei, Salonen Jarno, Urtti Arto, Cerullo Vincenzo, Hirvonen Jouni T, Santos Hélder A
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.
Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.
Adv Healthc Mater. 2020 Sep;9(17):e2000529. doi: 10.1002/adhm.202000529. Epub 2020 Jul 29.
Biohybrid nanosystems represent the cutting-edge research in biofunctionalization of micro- and nano-systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane-coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell-specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage-mediated uptake.
生物杂交纳米系统代表了微纳系统生物功能化领域的前沿研究。它们的物理化学性质在循环时间、躲避吞噬细胞以及新型抗原方面具有优势。这部分是蛋白质冠层质量差异以及在同源细胞中优先靶向和摄取的结果。然而，细胞膜对细胞内吞机制和时间的影响尚未得到充分评估。在此，通过定量流式细胞术分析，在存在不同摄取途径化学抑制剂的情况下，评估亲水性、带负电荷的多孔硅纳米颗粒及其膜包被对应物的内吞作用。主成分分析用于分析所有数据并推断模式，以突出内吞机制中的细胞特异性差异。此外，研究了裸颗粒和包被颗粒之间静态蛋白质冠层组成的差异，以及这些差异如何影响与人类巨噬细胞的相互作用。总体而言，细胞膜的存在仅影响纳米颗粒与细胞结合的速度和程度，而对内吞途径、蛋白质冠层组成没有直接影响，也不会减少巨噬细胞介导的摄取。
