Tuning the Selectivity of Dendron Micelles Through Variations of the Poly(ethylene glycol) Corona

Ryan M. Pearson; Soumyo Sen; Hao Jui Hsu; Matt Pasko; Marilyn Gaske; Petr Král; Seungpyo Hong

doi:10.1021/acsnano.6b02708

Tuning the Selectivity of Dendron Micelles Through Variations of the Poly(ethylene glycol) Corona

Ryan M. Pearson, Soumyo Sen, Hao Jui Hsu, Matt Pasko, Marilyn Gaske, Petr Král, Seungpyo Hong

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

Abstract

Engineering controllable cellular interactions into nanoscale drug delivery systems is key to enable their full potential. Here, using folic acid (FA) as a model targeting ligand and dendron micelles (DM) as a nanoparticle (NP) platform, we present a comprehensive experimental and modeling investigation of the structural properties of DMs that govern the formation of controllable, FA-mediated cellular interactions. Our experimental results demonstrate that a high level of control over the specific cell interactions of FA-targeted DMs can be achieved through modulation of the PEG corona length and the FA content. Using various molecular weight PEGs (0.6K, 1K, and 2K g/mol) and contents of dendron-FA conjugate incorporated into DMs (0, 5, 10, 25 wt %), the cell interactions of the targeted DMs could be controlled to exhibit minimal to >25-fold enhancement over nontargeted DMs. Molecular dynamics simulations indicated that structural characteristics, such as solvent accessible surface area of FA, local PEG density near FA, and FA mobility, account in part for the experimental differences in cellular interactions. The molecular structure that allows FA to depart from the surface of DMs to facilitate the initial cell surface binding was revealed to be the most important contributor for determining FA-mediated cellular interactions of DMs. The modular properties of DMs in controlling their specific cell interactions support the potential of DMs as a delivery platform and offer design cues for future development of targeted NPs.

Original language	English
Pages (from-to)	6905-6914
Number of pages	10
Journal	ACS Nano
Volume	10
Issue number	7
DOIs	https://doi.org/10.1021/acsnano.6b02708
Publication status	Published - 2016 Jul 26

Bibliographical note

Funding Information:
This study was supported by the Hans W. Vahlteich Research Fund from the University of Illinois at Chicago (UIC), NCI/NIH (grant no. 1R01CA182528), NSF (grant no. DMR-1409161), Alexs Lemonade Stand Foundation for Childhood Cancer, and Leukemia and Lymphoma Society. The MD simulation work was supported by NSF (grant no. DMR-1309765) and the UIC?LAS Award for Faculty in the Sciences.The research was conducted in a facility constructed with support from the NIH (grant C06RR15482). R.M.P. was partially supported by the Deans Scholarship from UIC. M.G. was supported by LASURI and the support from the Camille and Henry Dreyfus Foundation through the Senior Scientist Mentor Award to Prof. Cynthia J. Jameson.

Publisher Copyright:
© 2016 American Chemical Society.

All Science Journal Classification (ASJC) codes

Materials Science(all)
Engineering(all)
Physics and Astronomy(all)

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10.1021/acsnano.6b02708

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title = "Tuning the Selectivity of Dendron Micelles Through Variations of the Poly(ethylene glycol) Corona",

abstract = "Engineering controllable cellular interactions into nanoscale drug delivery systems is key to enable their full potential. Here, using folic acid (FA) as a model targeting ligand and dendron micelles (DM) as a nanoparticle (NP) platform, we present a comprehensive experimental and modeling investigation of the structural properties of DMs that govern the formation of controllable, FA-mediated cellular interactions. Our experimental results demonstrate that a high level of control over the specific cell interactions of FA-targeted DMs can be achieved through modulation of the PEG corona length and the FA content. Using various molecular weight PEGs (0.6K, 1K, and 2K g/mol) and contents of dendron-FA conjugate incorporated into DMs (0, 5, 10, 25 wt %), the cell interactions of the targeted DMs could be controlled to exhibit minimal to >25-fold enhancement over nontargeted DMs. Molecular dynamics simulations indicated that structural characteristics, such as solvent accessible surface area of FA, local PEG density near FA, and FA mobility, account in part for the experimental differences in cellular interactions. The molecular structure that allows FA to depart from the surface of DMs to facilitate the initial cell surface binding was revealed to be the most important contributor for determining FA-mediated cellular interactions of DMs. The modular properties of DMs in controlling their specific cell interactions support the potential of DMs as a delivery platform and offer design cues for future development of targeted NPs.",

author = "Pearson, {Ryan M.} and Soumyo Sen and Hsu, {Hao Jui} and Matt Pasko and Marilyn Gaske and Petr Kr{\'a}l and Seungpyo Hong",

note = "Funding Information: This study was supported by the Hans W. Vahlteich Research Fund from the University of Illinois at Chicago (UIC), NCI/NIH (grant no. 1R01CA182528), NSF (grant no. DMR-1409161), Alexs Lemonade Stand Foundation for Childhood Cancer, and Leukemia and Lymphoma Society. The MD simulation work was supported by NSF (grant no. DMR-1309765) and the UIC?LAS Award for Faculty in the Sciences.The research was conducted in a facility constructed with support from the NIH (grant C06RR15482). R.M.P. was partially supported by the Deans Scholarship from UIC. M.G. was supported by LASURI and the support from the Camille and Henry Dreyfus Foundation through the Senior Scientist Mentor Award to Prof. Cynthia J. Jameson. Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

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AU - Gaske, Marilyn

AU - Král, Petr

AU - Hong, Seungpyo

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N2 - Engineering controllable cellular interactions into nanoscale drug delivery systems is key to enable their full potential. Here, using folic acid (FA) as a model targeting ligand and dendron micelles (DM) as a nanoparticle (NP) platform, we present a comprehensive experimental and modeling investigation of the structural properties of DMs that govern the formation of controllable, FA-mediated cellular interactions. Our experimental results demonstrate that a high level of control over the specific cell interactions of FA-targeted DMs can be achieved through modulation of the PEG corona length and the FA content. Using various molecular weight PEGs (0.6K, 1K, and 2K g/mol) and contents of dendron-FA conjugate incorporated into DMs (0, 5, 10, 25 wt %), the cell interactions of the targeted DMs could be controlled to exhibit minimal to >25-fold enhancement over nontargeted DMs. Molecular dynamics simulations indicated that structural characteristics, such as solvent accessible surface area of FA, local PEG density near FA, and FA mobility, account in part for the experimental differences in cellular interactions. The molecular structure that allows FA to depart from the surface of DMs to facilitate the initial cell surface binding was revealed to be the most important contributor for determining FA-mediated cellular interactions of DMs. The modular properties of DMs in controlling their specific cell interactions support the potential of DMs as a delivery platform and offer design cues for future development of targeted NPs.

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Tuning the Selectivity of Dendron Micelles Through Variations of the Poly(ethylene glycol) Corona

Abstract

Bibliographical note

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