Effect of Protein Corona on the Drug Delivery of Carbogenic Nanodots and Their Mapping by Fluorescence Lifetime Imaging Microscopy

It is practically impossible to avoid the nonspecific binding of protein to a nanocarrier when it enters a biological fluid. This hinders the chemotherapeutic efficacy of the nanocarrier to a large extent. Surface functionalization, in the recent past, helped in reducing such nonspecific interactions. However, there is a lack of understanding as to how they help in the case of nanocarriers with size <6 nm. Here, we show that the glutathione and folic acid functionalization to a small carbogenic nanocarrier leads to substantial improvement in cell internalization and chemotherapeutic efficacy. The functionalization on smaller size of the nanocarrier helped in manipulating the binding affinity of the protein, which in turn helped in easy dynamic exchange with the surrounding environment. Using fluorescence lifetime imaging, we directly visualized and mapped the released drug at a very high resolution and provide a comprehensive mechanism of the drug distribution inside a cancer cell, as a consequence of the different affinity of protein corona on the carbon nanoparticle.