Gaining precise dynamics over the cellular entry of targeted nano-drug may be the most pertinent question in achieving high efficiency nano-drug. Based on force tracing technique, the dynamics of delivering targeted nano-drug into cell was explored.

Carbon dots (CDs) evoke a great deal of attention in biomedicine because of their unique properties. As an emerging theranostic agent, the CDs transmembrane transport process is the first and the most important step. Herein, a transmembrane dynamic process of transporting single CDs with folic acid into normal cells (Vero) and cancer cells (HeLa) were tracked by means of a force tracing technique based on atomic force microscopy. Meanwhile, the kinetic parameters of the the transmembrane process were measured and calculated. Interestingly, in the comparison between cancer cells (HeLa) and normal cells (Vero), the transporting force of single CDs with folic acid was smaller and the transporting average speed was slower.

Gold nanocages (Au NCs), as drug carriers, have been widely applied for cancer diagnosis and photothermal therapy (PTT). Transmembrane transporting efficacy of Au NCs is the fundamental and important issue for their use in PTT. Herein, we used a force tracing technique based on atomic force microscopy to track the dynamic transmembrane process of Au NCs at the single-particle level in real time. Meanwhile, we measured and compared the dynamic parameters of Au NCs with sizes of 50 and 100 nm usually used as nanodrug carriers of PTT. It is concluded that the 50 nm Au NC transmembrane transporting needs smaller force and shorter duration with a much faster speed. However, both the 50 and 100 nm Au NC transmembrane transporting depends on the caveolin-mediated endocytosis, clathrin-mediated endocytosis, and macropinocytosis, which was also confirmed by confocal fluorescence imaging. This report will provide a potential technique for screening nanodrug carriers from the perspective of transmembrane transporting efficacy.

Based on the force tracing technique, the dynamic trans-membrane transport process of single SiNPs in living cells was monitored.