Programmed packaging of mesoporous silica nanocarriers for matrix metalloprotease 2-triggered tumor targeting and release

摘要: The development of multifunctional nanocarrier with each unit functioning at the correct time and location is a challenge for clinical applications. With this in mind, type intelligent mesoporous silica (PGFMSN) proposed matrix metalloprotease 2 (MMP 2)-triggered tumor targeting release by integrating programmed packing MMP 2-degradable gelatin. Mesoporous nanoparticles (MSN) are first functionalized folic acid (FA) as target ligand to improve cell uptake. Then gelatin introduced onto FA-MSN via temperature-induced gelation, where layer blocks drugs inside mesopores protects ligand. To prolong blood-circulation lifetime, PEG further decorated obtain PGFMSN. All units programmatically incorporated simple way coordinated an optimal fashion. Cells, multicellular spheroids vivo results demonstrate that PGFMSN shielded against nonspecific After circulating tissue, up-regulated MMP-2 hydrolyzes deshield switch on function FA, which facilitate selective uptake cells through folate-receptor-mediated endocytosis. Meanwhile, packaged drug released due shedding layer. It shown doxorubicin (DOX)-loaded exhibits superior targeting, internalization, cytotoxicity, antitumor efficacy over free DOX, non-PEGylated non-targeted nanoparticles, provides potential applications targeted cancer therapy.