title: Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles.
abstract: Polymeric nanoparticles (NPs) and dendrimers are two major classes of nanomaterials that have demonstrated great potential for targeted drug delivery. However, their targeting efficacy has not yet met clinical needs, largely because of a lack of control over their targeting kinetics, which often results in rapid clearance and off-target drug delivery. To address this issue, we have designed a novel hybrid NP (nanohybrid) platform that allows targeting kinetics to be effectively controlled through hybridization of targeted dendrimers with polymeric NPs. Folate (FA)-targeted generation 4 poly(amidoamine) dendrimers were encapsulated into poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) NPs using a double emulsion method, forming nanohybrids with a uniform size (~100 nm in diameter) at high encapsulation efficiencies (69-85%). Targeted dendrimers encapsulated within the NPs selectively interacted with FA receptor (FR)-overexpressing KB cells upon release in a temporally controlled manner. The targeting kinetics of the nanohybrids were modulated using three different molecular weights (MW) of the PLA block (23, 30, and 45 kDa). The release rates of the dendrimers from the nanohybrids were inversely proportional to the MW of the PLA block, which dictated their binding and internalization kinetics with KB cells. Our results provide evidence that selective cellular interactions can be kinetically controlled by the nanohybrid design, which can potentially enhance targeting efficacy of nanocarriers.
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, United States.
authors.forename: Suhair
authors.initials: S
authors.lastname: Sunoqrot
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Bae
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Pearson
authors.forename: Kevin
authors.initials: K
authors.lastname: Shyu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Seungpyo
authors.initials: S
authors.lastname: Hong
mesh_terms: D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D007624:KB Cells; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors
chemical_list: D050091:Dendrimers; C092361:poly(ethylene glycol) lysine copolymer; D011092:Polyethylene Glycols; D005492:Folic Acid; D008239:Lysine