Engineering Chimeric Receptors To Investigate the Size- and Rigidity-Dependent Interaction of PEGylated Nanoparticles with Cells

Wei-Chiao Huang, Pierre-Alain Burnouf, Yu-Cheng Su, Bing-Mae Chen, Kuo-Hsiang Chuang, Chia-Wei Lee, Pei-Kuen Wei, Tian-Lu Cheng, Steve R Roffler

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Attachment of ligands to the surface of nanoparticles (NPs) is an attractive approach to target specific cells and increase intracellular delivery of nanocargos. To expedite investigation of targeted NPs, we engineered human cancer cells to express chimeric receptors that bind polyethylene glycol (PEG) and internalize stealth NPs in a fashion similar to ligand-targeted liposomes against epidermal growth factor receptor 1 or 2 (HER1 or HER2), which are validated targets for cancer therapy. Measurement of the rate of endocytosis and lysosomal accumulation of small (80-94 nm) or large (180-220 nm) flexible liposomes or more rigid lipid-coated mesoporous silica particles in human HT29 colon cancer and SKBR3 breast cancer cells that express chimeric receptors revealed that larger and more rigid NPs were internalized more slowly than smaller and more flexible NPs. An exception is when both the small and large liposomes underwent endocytosis via HER2. HER1 mediated faster and greater uptake of NPs into cells but retained NPs less well as compared to HER2. Lysosomal accumulation of NPs internalized via HER1 was unaffected by NP rigidity but was inversely related to NP size, whereas large rigid NPs internalized by HER2 displayed increased lysosomal accumulation. Our results provide insight into the effects of NP properties on receptor-mediated endocytosis and suggest that anti-PEG chimeric receptors may help accelerate investigation of targeted stealth NPs.

Original languageEnglish
Pages (from-to)648-62
Number of pages15
JournalACS Nano
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 13 2016

Fingerprint

rigidity
Rigidity
engineering
Nanoparticles
nanoparticles
cells
interactions
Liposomes
cancer
Polyethylene glycols
glycols
polyethylenes
Ligands
Cells
ligands
Epidermal Growth Factor Receptor
breast
Silicon Dioxide
Lipids
attachment

Keywords

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Engineering Chimeric Receptors To Investigate the Size- and Rigidity-Dependent Interaction of PEGylated Nanoparticles with Cells. / Huang, Wei-Chiao; Burnouf, Pierre-Alain; Su, Yu-Cheng; Chen, Bing-Mae; Chuang, Kuo-Hsiang; Lee, Chia-Wei; Wei, Pei-Kuen; Cheng, Tian-Lu; Roffler, Steve R.

In: ACS Nano, Vol. 10, No. 1, 13.01.2016, p. 648-62.

Research output: Contribution to journalArticle

Huang, W-C, Burnouf, P-A, Su, Y-C, Chen, B-M, Chuang, K-H, Lee, C-W, Wei, P-K, Cheng, T-L & Roffler, SR 2016, 'Engineering Chimeric Receptors To Investigate the Size- and Rigidity-Dependent Interaction of PEGylated Nanoparticles with Cells', ACS Nano, vol. 10, no. 1, pp. 648-62. https://doi.org/10.1021/acsnano.5b05661
Huang, Wei-Chiao ; Burnouf, Pierre-Alain ; Su, Yu-Cheng ; Chen, Bing-Mae ; Chuang, Kuo-Hsiang ; Lee, Chia-Wei ; Wei, Pei-Kuen ; Cheng, Tian-Lu ; Roffler, Steve R. / Engineering Chimeric Receptors To Investigate the Size- and Rigidity-Dependent Interaction of PEGylated Nanoparticles with Cells. In: ACS Nano. 2016 ; Vol. 10, No. 1. pp. 648-62.
@article{40ccde03e43a4d2dae3419a7ca45b5f5,
title = "Engineering Chimeric Receptors To Investigate the Size- and Rigidity-Dependent Interaction of PEGylated Nanoparticles with Cells",
abstract = "Attachment of ligands to the surface of nanoparticles (NPs) is an attractive approach to target specific cells and increase intracellular delivery of nanocargos. To expedite investigation of targeted NPs, we engineered human cancer cells to express chimeric receptors that bind polyethylene glycol (PEG) and internalize stealth NPs in a fashion similar to ligand-targeted liposomes against epidermal growth factor receptor 1 or 2 (HER1 or HER2), which are validated targets for cancer therapy. Measurement of the rate of endocytosis and lysosomal accumulation of small (80-94 nm) or large (180-220 nm) flexible liposomes or more rigid lipid-coated mesoporous silica particles in human HT29 colon cancer and SKBR3 breast cancer cells that express chimeric receptors revealed that larger and more rigid NPs were internalized more slowly than smaller and more flexible NPs. An exception is when both the small and large liposomes underwent endocytosis via HER2. HER1 mediated faster and greater uptake of NPs into cells but retained NPs less well as compared to HER2. Lysosomal accumulation of NPs internalized via HER1 was unaffected by NP rigidity but was inversely related to NP size, whereas large rigid NPs internalized by HER2 displayed increased lysosomal accumulation. Our results provide insight into the effects of NP properties on receptor-mediated endocytosis and suggest that anti-PEG chimeric receptors may help accelerate investigation of targeted stealth NPs.",
keywords = "Journal Article, Research Support, Non-U.S. Gov't, HER1; HER2; PEGylated liposomes; caveolin; clathrin-mediated endocytosis; immunoliposomes; polyethylene glycol; stealth NPs; αPEG antibody",
author = "Wei-Chiao Huang and Pierre-Alain Burnouf and Yu-Cheng Su and Bing-Mae Chen and Kuo-Hsiang Chuang and Chia-Wei Lee and Pei-Kuen Wei and Tian-Lu Cheng and Roffler, {Steve R}",
year = "2016",
month = "1",
day = "13",
doi = "10.1021/acsnano.5b05661",
language = "English",
volume = "10",
pages = "648--62",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

T1 - Engineering Chimeric Receptors To Investigate the Size- and Rigidity-Dependent Interaction of PEGylated Nanoparticles with Cells

AU - Huang, Wei-Chiao

AU - Burnouf, Pierre-Alain

AU - Su, Yu-Cheng

AU - Chen, Bing-Mae

AU - Chuang, Kuo-Hsiang

AU - Lee, Chia-Wei

AU - Wei, Pei-Kuen

AU - Cheng, Tian-Lu

AU - Roffler, Steve R

PY - 2016/1/13

Y1 - 2016/1/13

N2 - Attachment of ligands to the surface of nanoparticles (NPs) is an attractive approach to target specific cells and increase intracellular delivery of nanocargos. To expedite investigation of targeted NPs, we engineered human cancer cells to express chimeric receptors that bind polyethylene glycol (PEG) and internalize stealth NPs in a fashion similar to ligand-targeted liposomes against epidermal growth factor receptor 1 or 2 (HER1 or HER2), which are validated targets for cancer therapy. Measurement of the rate of endocytosis and lysosomal accumulation of small (80-94 nm) or large (180-220 nm) flexible liposomes or more rigid lipid-coated mesoporous silica particles in human HT29 colon cancer and SKBR3 breast cancer cells that express chimeric receptors revealed that larger and more rigid NPs were internalized more slowly than smaller and more flexible NPs. An exception is when both the small and large liposomes underwent endocytosis via HER2. HER1 mediated faster and greater uptake of NPs into cells but retained NPs less well as compared to HER2. Lysosomal accumulation of NPs internalized via HER1 was unaffected by NP rigidity but was inversely related to NP size, whereas large rigid NPs internalized by HER2 displayed increased lysosomal accumulation. Our results provide insight into the effects of NP properties on receptor-mediated endocytosis and suggest that anti-PEG chimeric receptors may help accelerate investigation of targeted stealth NPs.

AB - Attachment of ligands to the surface of nanoparticles (NPs) is an attractive approach to target specific cells and increase intracellular delivery of nanocargos. To expedite investigation of targeted NPs, we engineered human cancer cells to express chimeric receptors that bind polyethylene glycol (PEG) and internalize stealth NPs in a fashion similar to ligand-targeted liposomes against epidermal growth factor receptor 1 or 2 (HER1 or HER2), which are validated targets for cancer therapy. Measurement of the rate of endocytosis and lysosomal accumulation of small (80-94 nm) or large (180-220 nm) flexible liposomes or more rigid lipid-coated mesoporous silica particles in human HT29 colon cancer and SKBR3 breast cancer cells that express chimeric receptors revealed that larger and more rigid NPs were internalized more slowly than smaller and more flexible NPs. An exception is when both the small and large liposomes underwent endocytosis via HER2. HER1 mediated faster and greater uptake of NPs into cells but retained NPs less well as compared to HER2. Lysosomal accumulation of NPs internalized via HER1 was unaffected by NP rigidity but was inversely related to NP size, whereas large rigid NPs internalized by HER2 displayed increased lysosomal accumulation. Our results provide insight into the effects of NP properties on receptor-mediated endocytosis and suggest that anti-PEG chimeric receptors may help accelerate investigation of targeted stealth NPs.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - HER1; HER2; PEGylated liposomes; caveolin; clathrin-mediated endocytosis; immunoliposomes; polyethylene glycol; stealth NPs; αPEG antibody

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-84991245579&origin=resultslist&sort=plf-f&src=s&st1=Engineering+Chimeric+Receptors+To+Investigate+the+Size-+and+Rigidity-Dependent+Interaction+of+PEGylated+Nanoparticles+with+Cells&st2=&sid=4aa52cc51d325dfdad84a793f8c14f1c&sot=b&sdt=b&sl=143&s=TITLE-ABS-KEY%28Engineering+Chimeric+Receptors+To+Investigate+the+Size-+and+Rigidity-Dependent+Interaction+of+PEGylated+Nanoparticles+with+Cells%29&relpos=0&citeCnt=3&searchTerm=

UR - https://www.scopus.com/results/citedbyresults.uri?sort=plf-f&cite=2-s2.0-84991245579&src=s&imp=t&sid=11f7ddfd29f2b100974dfbbd5137fb74&sot=cite&sdt=a&sl=0&origin=recordpage&editSaveSearch=&txGid=c158432de0431abd43a8e886213f3255

U2 - 10.1021/acsnano.5b05661

DO - 10.1021/acsnano.5b05661

M3 - Article

C2 - 26741147

VL - 10

SP - 648

EP - 662

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 1

ER -