Modification of calcium carbonate based gene and drug delivery systems by a cell-penetrating peptide

Abstract

In this study, a facile strategy to effectively improve the gene and drug delivery efficiencies of calcium carbonate based nanoparticles was developed by introducing a cell-penetrating peptide, KALA, into the delivery systems. To evaluate the effect of KALA on the gene delivery efficiency, luciferase reporter gene plasmid was encapsulated in CaCO₃–KALA–DNA nanoparticles. The measurements of a Zetasizer showed that the size and the zeta potential of CaCO₃–KALA–DNA nanoparticles increased with increasing KALA amount because of the addition of positively charged KALA. Due to the existence of KALA, the gene expressions could be significantly enhanced in both HeLa and 293T cells. Confocal microscopy observation showed that the cellular uptake of CaCO₃–KALA–DNA nanoparticles was obviously enhanced compared to CaCO₃–DNA nanoparticles. To investigate the gene and drug co-delivery property, p53 expression plasmid and doxorubicin hydrochloride (DOX) were loaded in CaCO₃–KALA–p53–DOX nanoparticles. The in vitro cell growth inhibition effect of CaCO₃–KALA–p53–DOX nanoparticles was evaluated by MTT assay. Compared with CaCO₃–p53–DOX nanoparticles, CaCO₃–KALA–p53–DOX nanoparticles exhibited enhanced delivery efficiency, which led to a stronger inhibition effect on HeLa cells. These results indicated that the addition of KALA, which facilitated the cellular uptake of various agents, could improve both gene and drug delivery efficiencies. The KALA modified CaCO₃ based nanoparticles have promising applications in cancer treatments.