Traceless protein delivery with an efficient recyclable nanocarrier

Intracellular delivery is a prerequisite for the efficacy of many pharmaceutical proteins. Herein, vitamin B6 (pyridoxal-5′-phosphate, PLP) functionalized calcium phosphate (CP) is used as the bio-recyclable nanocarrier for delivery of proteins into cells. Proteins could be loaded on/released from PLP-CP via formation/hydrolysis of pH sensitive aldimine bridging lysine and surface-displayed PLP. The loaded proteins could be delivered into the cytosol of HeLa, HepG2 and L929 cells where the carrier could be metabolized into endogenous metabolites of Ca2+, HPO42−, and vitamin B6. PLP-CP mediated cell transduction is 10–40 folds more efficient than TAT which is a widely used cell penetrating peptide, demonstrating the utility of PLP-CP as the traceless platform for high-efficiency delivery of proteins into mammalian cells.