Spatial controlled multistage nanocarriers through hybridization of dendrimers and gelatin nanoparticles for deep penetration and therapy into tumor tissue

A spatially controlled multistage nanocarrier with small polyamidoamine (PAMAM) dendrimers (~5 nm) encapsulating into large gelatin NPs (~200 nm). With an outer gelatin layer to act as a shield, these multistage nanocarriers were more stable during systematic circulation for their relatively large particle size and electrically neutral surface, than positively charged PAMAM dendrimers alone. However, gelatin NPs were degraded via matrix metalloproteinase-2 (MMP-2) enzymes in tumor tissue, triggering an internal release of PAMAM dendrimers that possessed small particle sizes and a positive charge, which guaranteed improved subsequent deep penetration and high intracellular uptake into tumor cells through electrostatic adsorptive endocytosis.364