Drug-loaded lipid-coated hybrid organic-inorganic “stealth” nanoparticles for cancer therapy

Hybrid porous nanoscale metal organic frameworks (nanoMOFs) made of iron trimesate are attracting increasing interest as drug carriers, due to their high drug loading capacity, biodegradability, and biocompatibility. NanoMOF surface modification to prevent clearance by the innate immune system remains still challenging in reason of their high porosity and biodegradable character. Herein, FDA-approved lipids and poly(ethylene glycol) (PEG)-lipid conjugates were used to engineer the surface of nanoMOFs by a rapid and convenient solvent-exchange deposition method. The resulting lipid-coated nanoMOFs were extensively characterized. For the first time, we show that nanoMOF surface modification with lipids affords a better control over drug release and their degradation in biological media. Moreover, when loaded with the anticancer drug Gem-MP (Gemcitabine-monophosphate), iron trimesate nanoMOFs acted as “Trojan horses” carrying the drug inside cancer cells to eradicate them. Most interestingly, the PEG-coated nanoMOFs escaped the capture by macrophages. In a nutshell, versatile PEG-based lipid shells control cell interactions and open perspectives for drug targeting.