Targeted Delivery of Metformin Against Lung Cancer Cells Via Hyaluronan-Modified Mesoporous Silica Nanoparticles

Metformin (Metf), a biguanide widely used to manage type 2 diabetes mellitus, has recently entered the spotlight as a hopeful anti-tumor agent. In this work, because of the hyaluronic acid (HA) capability to specifically target CD44 receptors over-expressed on the surface of non-small lung cancer cells, a tumor-targeted drug delivery nanocarrier-based HA-coated mesoporous silica nanoparticles (MSNs) have been used for active targeting and efficient delivery of Metf. For this purpose, the synthesized MSNs-HA were characterized using BET, FE-EM, DLS, and FTIR. Confocal microscopy was applied to show the enhanced cellular uptake of the FITC-labelled MSNs-HA compared to MSNs without HA coating. MTT and qPCR results also revealed superior cytotoxicity and pro-apoptotic effects of Metf-loaded MSNs-HA (Metf@MSNs-HA) against the A549 lung cancer cells compared to the free Metf and MSNs@Metf due to the efficient CD44-targeting capability and delivery of Metf@MSNs-HA. Besides, it was demonstrated that Metf@MSNs-HA could effectively trigger the AMP-activated protein kinase alpha (AMPK alpha) pathway and inhibit the mammalian target rapamycin (mTOR), increasing the growth suppression. In conclusion, this preliminary work disclosed the great potential of Metf@MSNs-HA in targeted therapy of lung cancer cells.