Improving Tumor Targeting of Exosomal Membrane-Coated Polymeric Nanoparticles by Conjugation with Aptamers

The coating of natural cellular or exosomal membranes (EMs) onto polymeric nanoparticles has become essential in extending the circulation half-time of nanoparticles by escaping from immune surveillance. Here we report on the surface modification of EM-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles by AS1411 aptamers (AS-EP) for improved tumor targeting. The combination of microfluidic sonication and cholesterol-modified aptamer functionalization allows for assembly of AS-EP within 10 min. The resulting AS-EP shows a prolonged in vivo circulation time benefiting from the natural properties of exosomes and exhibits high tumor targeting efficiency through specific binding of AS1411 aptamers to nucleolin on the membrane of tumor cells. Moreover, intravenous administration of AS-EP to mice will not result in abnormal pathology or hemolysis. This work opens up opportunities to fabricate and functionalize biomembrane-coated nanoparticles for targeted drug delivery applications.