Folic acid (FA)-conjugated mesoporous silica nanoparticles combined with MRP-1 siRNA improves the suppressive effects of myricetin on non-small cell lung cancer (NSCLC).

Non-small cell lung cancer (NSCLC) is a common diagnosed cancer disease worldwide and its management remains a challenge. Synergistic cancer therapeutic strategy is interesting for multiple advantages, such as excellent targeting accuracy, low side effects, and promoted therapeutic efficiency. In the present study, myricetin (Myr)-loaded mesoporous silica nanoparticles (MSN) combined with multidrug resistance protein (MRP-1) siRNA was prepared. The surface of the synthesized nanoparticles was modified with folic acid (FA) to promote the therapeutic efficiency of Myr for the treatment of NSCLC. The collected particles were nano-sized and showed a sustained release of Myr in the physiological conditions. FA-conjugated nanoformulations displayed a significant uptake in lung cancer cells compared with that of the non-targeted nanoparticles. The in vitro drug release results suggested a sustained release in FA-conjugated MSN with Myr and MRP-1 nanoparticles compared to the free Myr and MSN combined with MRP-1/Myr. Treatments with FA-conjugated MSN combined with Myr and MRP-1 markedly reduced the cell viability of lung cancer cell lines, including A549 and NCI-H1299, which was accompanied with the decreased number of colony formation. In addition, FA-conjugated MSN loaded with Myr and MRP-1 significantly induced apoptosis in lung cancer cells, along with up-regulated expression levels of cleaved Caspase-3 and PARP. In vivo fluorescence results demonstrated that FA-conjugated MSN with Myr and MRP-1 nanoparticles could specifically accumulate at tumor sites. Compared with free Myr and MSN combined with MRP-1/Myr nanoparticles, FA-conjugated MSN loaded with Myr and MRP-1 nanoparticles could more effectively suppress tumor growth with little side effects. Overall, FA-conjugated nanoparticulate system could provide a novel and effective platform for the treatment of NSCLC.