Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles

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 res...

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Main Authors: Sunoqrot, Suhair, Bae, Jin Woo, Shyu, Kevin, Liu, Ying, Kim, Dong-Hwan, Hong, Seungpyo, Pearson, Ryan M.
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2013
Online Access:https://hdl.handle.net/10356/98957
http://hdl.handle.net/10220/12814
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author Sunoqrot, Suhair
Bae, Jin Woo
Shyu, Kevin
Liu, Ying
Kim, Dong-Hwan
Hong, Seungpyo
Pearson, Ryan M.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Sunoqrot, Suhair
Bae, Jin Woo
Shyu, Kevin
Liu, Ying
Kim, Dong-Hwan
Hong, Seungpyo
Pearson, Ryan M.
author_sort Sunoqrot, Suhair
collection NTU
description 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.
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spelling ntu-10356/989572022-02-16T16:28:54Z Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles Sunoqrot, Suhair Bae, Jin Woo Shyu, Kevin Liu, Ying Kim, Dong-Hwan Hong, Seungpyo Pearson, Ryan M. School of Chemical and Biomedical Engineering 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. 2013-08-02T02:21:51Z 2019-12-06T20:01:29Z 2013-08-02T02:21:51Z 2019-12-06T20:01:29Z 2012 2012 Journal Article Sunoqrot, S., Bae, J. W., Pearson, R. M., Shyu, K., Liu, Y., Kim, D. H.,& Hong, S. (2012). Temporal Control over Cellular Targeting through Hybridization of Folate-targeted Dendrimers and PEG-PLA Nanoparticles. Biomacromolecules, 13(4), 1223-1230. https://hdl.handle.net/10356/98957 http://hdl.handle.net/10220/12814 10.1021/bm300316n 22439905 en Biomacromolecules
spellingShingle Sunoqrot, Suhair
Bae, Jin Woo
Shyu, Kevin
Liu, Ying
Kim, Dong-Hwan
Hong, Seungpyo
Pearson, Ryan M.
Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles
title Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles
title_full Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles
title_fullStr Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles
title_full_unstemmed Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles
title_short Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles
title_sort temporal control over cellular targeting through hybridization of folate targeted dendrimers and peg pla nanoparticles
url https://hdl.handle.net/10356/98957
http://hdl.handle.net/10220/12814
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