Conjugation of folic acid onto poly (acrylic acid-co-allylamine)-grafted mesoporous silica nanoparticles for controlled methotrexate delivery

A new drug delivery system (DDS) was designed using mesoporous silica nanoparticles functionalized with a copolymer of poly(acrylic acid-co-allylamine) conjugated with folic acid. DDS was developed to enable targeted and controlled delivery of methotrexate to cancer cells. The DDS pores were utilized for loading methotrexate through multilayer physical adsorption, which occurred spontaneously and exothermically. The methotrexate adsorption capacity of the DDS was 673.001 ± 4.518 mg/g. The copolymer acted as a gatekeeper, regulating the entry and exit of methotrexate from the pores. The DDS exhibited minimal methotrexate leakage at high pH levels but showed a significantly increased release at lower pH levels, demonstrating a pH-controlled drug release pattern. Mathematical modeling indicated that diffusion played a major role in drug release, and the DDS functioned as a reservoir system with a declining release rate over time. Importantly, the DDS displayed significant cytocompatibility, as demonstrated by MTT assays. Furthermore, the methotrexate-loaded DDS showed remarkable efficacy in killing MCF-7 cells, suggesting that folic acid facilitates DDS-specific targeting of MCF-7 cells via folic acid receptors.