The combined effects of size and surface chemistry on the accumulation of boronic acid-rich protein nanoparticles in tumors.

The high drug concentration and long-acting time within tumor tissues are a key challenge in cancer treatment. Here we prepare the boronic acid-rich bovine serum albumin nanoparticles with the size of 70 nm, 110 nm and 150 nm, and subsequently decorate particle surface with polyethyleneimine-polyethylene glycol copolymer and cRGD peptide. We demonstrated that the drug accumulation and particle residence time at tumor site can be significantly improved by incorporating boronic acid group into the bovine serum albumin nanoparticles, optimizing particle size and decorating particle surface. We show that the size- and surface chemistry-driven dual-actions lead to the doxorubicin accumulation at tumor site go beyond 12% injected dose per gram of tumor through such delivery system, which is 16-fold higher than that of free doxorubicin injected. Based on the systemic, tissue and cell level analysis, we demonstrated that the incorporated boronic acid group into the nanoparticles enhances the recognition ability of nanoparticles to cancer cells, and prolongs the action time of nanoparticles at tumor sites since the boronic acid group can reversibly and rapidly react with sialic acid residues which are overexpressed in cancer cells. These features make that this drug delivery system not only has significantly superior ability in impeding tumor growth, but also induces distinct shrinkage and apoptosis of tumor.