A pH-sensitive polymer based precise tumor targeting strategy with reduced uptake of nanoparticles by non-cancerous cells. Issue 39 (18th September 2019) - Li, Zihou
Abstract : A T 2 -weighted MRI contrast agent (SPION-AN-FA@mPEG) can precisely target cancer cells with folate receptor α (FRα) diminishing non-specific uptake by normal healthy cells. Abstract : Drug-loaded nanoparticles can be specifically uptaken by tumor cells to realize active targeting due to the conjugated ligands or antibodies on their surface. However, some non-cancerous cells express non-specific receptors or antigens on their surface, which can react with the ligands or antibodies conjugated on the nanoparticle surface and then result in non-specific uptake of the nanoparticles by non-cancerous cells. In order to reduce the non-specific uptake of nanoparticles by non-cancerous cells, in this study, we proposed a pH-sensitive polymer based precise tumor targeting strategy and synthesized superparamagnetic iron oxide nanoparticle (SPION) encapsulated albumin nanoparticles (AN) with conjugation of folic acid (FA) and mPEG–DCA (SPION-AN-FA@mPEG), in which mPEG can shield FA, avoiding the non-specific recognition by normal cells under physiological conditions, and can be shed to expose FA in tumor microenvironments. The pH-sensitivity of mPEG–DCA was verified by HPLC characterization and 1 H-NMR spectroscopy. The graft density and length of mPEG–DCA were optimized via the cellular uptake of SPION-AN-FA@mPEG measured by flow cytometry analysis. The r 2 value and r 2 / r 1 ratio of the optimized SPION-AN-FA@mPEG ( i.e., SPION-AN-FA@mPEG4) are 168.6 mM −1 s −1 and 42.8, respectively, which are both much higher than that of the commercial contrast agent Resovist®. The in vitro T 2 -weighted MR images and in vivo MRI performance demonstrate that our SPION-AN-FA@mPEG4 nanoparticles can be used as an effective T 2 -weighted MRI contrast agent.