| Carbon quantum dots,also referred to as carbon dots（CDs）,is a type of carbon nanomaterial.CDs evoke a great attention because of their excellent optical properties,stable chemical properties,good biocompatibility,low toxicity,good water solubility,high drug loading rate,and well surface passivation.As a drug carrier,CDs have been widely studied for loading drugs into cells.However,due to the spatial and temporal resolution limitations of technique,the dynamic transmembrane transport process of CDs as drug carriers is still elusive.Here,folic acid（FA）was modified onto the surface of CDs as a carrier for targeted drug carriers.Using single molecule force spectroscopy（SMFS）-based force tracing technique（which can measure forces as low as pN level,with microseconds time resolution）,we studied the transmembrane dynamic process of folate-modified carbon dot（FA-CDs）entering the cells.The dynamic process of FA-CDs transporting into living cells was record by force tracing technique in real time,measuring the force and duration required for FA-CDs transporting into cells and studying the FA-CDs transport mechanism.We also investigated the differences of dynamic parametres（transporting force,time,speed）for FA-CDs transporting into different cell lines（normal cell and cancer cell）.This paper will provide a theoretical basis for the design of nanomedicine（the size,loading rate,releasing drug time of nanomedicine）,which is of great significance in the field of biomedicine.The research progress is as follows:1.The transmembrane process of FA-CDs transporting into normal cell（Vero cell）was recorded,the force and duration required for CDs transport into Vero cells were calculated.The force distribution of FA-CDs transported into single Vero cell is in the range of 33-351 pN with an average of 79±23 pN,and the corresponding duration distribution is in the range of 2.5-65 ms with an average of 19±11 ms at a speed of 2.03μm s-1.2.Subsequently,blocking agents for different uptake pathways were used to study the mechanism of CDs transporting into Vero cells.The results showed that the way of Vero cells transporting CDs are mainly through the caveolin and clathrin-mediated endocytosis and the macropinocytosis pathway,in which caveolin-mediated endocytosis and macropinocytosis are the main pathways.3.The kinetics of the FA-CDs transported into cancer cells（HeLa cells）were investigated.The duration of the transporting event varies from 8.6 to 20.8 ms with the average value of 12.3±2.8 ms,and the corresponding force distributes from 20.2to 72.1 pN with the mean value of 33±12 pN,and the average speed is 1.76μm s-1.It is found that the transporting duration for the both cells is almost indentical.However,the transporting force for HeLa cell（33±12 pN）is smaller than that of Vero cells（79±50 pN）.Meanwhile,it is noted that the corresponding average speed(1.76μm s-1)is slightly slower comparing with Vero cells(2.03μm s-1).Both the smaller transporting force and slower transporting speed may be attributed to the FA-receptor mediated endocytosis of CDs.We speculate that this may be due to overexpression of the folate receptor（FR）on the surface of HeLa cells. |
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