iRGD-targeted hybrid nanoparticles reverses multi-drug resistant to effectively combat liver cancer

The off-target delivery as well as multi-drug resistance (MDR) are generally recognised as two keys difficulties responsible for the poor performance of chemotherapy in clinical treatment of cancer. With the aim to address the problems, we herein constructed iRGD modified and lipid-coated silica (LSC) nanoparticles co-delivering Ca²⁺ channel siRNA and adriamycin (Adr) to reverse the MDR in liver cancer (LSC/R-A). The iRGD decoration was suggested to elevate the tumour accumulation of the drug delivery system (DDS). In addition, the introduction of Ca²⁺ channel siRNA was proved to reverse the MDR within the cells of cancer by regulation the T-type Ca²⁺ channels. Our results showed that decreased expression of T-type Ca²⁺ channels resulted in lowered cytosolic Ca²⁺ level responsible for the cell cycle arrest (at G0/G1 phase) as well as elevated cellular drug retention in HepG2/Adr. B in vitro/in vivo experiments revealed that LSC/R-A exerted highly elevated therapeutic outcome on HepG2/Adr, than administration of single siRNA or Adr.