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.
authors.affiliation: Institute of Biomedical Science, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Science, Academia Sinica , Taipei 11529, Taiwan.|Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica , Taipei, Taiwan.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Burnouf
authors.affiliation: Institute of Biomedical Science, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Su
authors.affiliation: Institute of Biomedical Science, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Bing-Mae
authors.initials: BM
authors.lastname: Chen
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University , Taipei 110, Taiwan.
authors.forename: Kuo-Hsiang
authors.initials: KH
authors.lastname: Chuang
authors.affiliation: Research Center for Applied Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Research Center for Applied Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Pei-Kuen
authors.initials: PK
authors.lastname: Wei
authors.affiliation: Department of Biomedical and Environmental Biology, Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University , Kaohsiung 80708, Taiwan.
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Science, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Steve R
authors.initials: SR
authors.lastname: Roffler
mesh_terms: D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D060846:Cell Engineering; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D019073:HT29 Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D062165:Receptors, Artificial / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D051242:Caveolin 1; D066246:ErbB Receptors; D008081:Liposomes; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D062165:Receptors, Artificial; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: HER1; HER2; PEGylated liposomes; caveolin; clathrin-mediated endocytosis; immunoliposomes; polyethylene glycol; stealth NPs; αPEG antibody