Co-encapsulation of paclitaxel and 5-fluorouracil in folic acid-modified, lipid-encapsulated hollow mesoporous silica nanoparticles for synergistic breast cancer treatment

A dual-loaded multi-targeted drug delivery nanosystem was constructed to simultaneously load paclitaxel (PTX) and 5-fluorouracil (5-FU) for targeted delivery and sustained release at tumor sites. Hollow mesoporous silica nanoparticles (HMSNs) were prepared by the inverse microemulsion method, then modified with folic acid and pH- and temperature-responsive materials, co-loaded with PTX and 5-FU, and finally encapsulated into lipid membranes. The obtained nanosystem was selectively internalized by human breast cancer MCF-7 cells that overexpress folate receptors through an energy-dependent process, and it released both drugs in vitro in a simulated tumor microenvironment. Moreover, the inhibitory effect of the dual-loaded nanoparticles was significantly better than that of the free drugs, suggesting that the composite nanosystem has the potential to selectively target tumor sites and perform the synergistic effect of PTX and 5-FU, while reducing their toxic effects on normal tissues.