title: Using anti-poly(ethylene glycol) bioparticles for the quantitation of PEGylated nanoparticles.
abstract: Attachment of polyethylene glycol (PEG) molecules to nanoparticles (PEGylation) is a widely-used method to improve the stability, biocompatibility and half-life of nanomedicines. However, the evaluation of the PEGylated nanomedicine pharmacokinetics (PK) requires the decomposition of particles and purification of lead compounds before analysis by high performance liquid chromatography (HPLC), mass spectrometry, etc. Therefore, a method to directly quantify un-decomposed PEGylated nanoparticles is needed. In this study, we developed anti-PEG bioparticles and combined them with anti-PEG antibodies to generate a quantitative enzyme-linked immunosorbent assay (ELISA) for direct measurement of PEGylated nanoparticles without compound purification. The anti-PEG bioparticles quantitative ELISA directly quantify PEG-quantum dots (PEG-QD), PEG-stabilizing super-paramagnetic iron oxide (PEG-SPIO), Lipo-Dox and PEGASYS and the detection limits were 0.01 nM, 0.1 nM, 15.63 ng/mL and 0.48 ng/mL, respectively. Furthermore, this anti-PEG bioparticle-based ELISA tolerated samples containing up to 10% mouse or human serum. There was no significant difference in pharmacokinetic studies of radiolabeled PEG-nanoparticles (Nano-X-111In) through anti-PEG bioparticle-based ELISA and a traditional gamma counter. These results suggest that the anti-PEG bioparticle-based ELISA may provide a direct and effective method for the quantitation of any whole PEGylated nanoparticles without sample preparation.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan first Road, Kaohsiung 80708, Taiwan.
authors.forename: Yuan-Chin
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, 100 Shih-Chuan First Road, Kaohsiung 80708, Taiwan.
authors.forename: Ta-Chun
authors.initials: TC
authors.lastname: Cheng
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences and Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences and Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jia-Je
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Lin
authors.affiliation: Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, 100 Shih-Chuan First Road, Kaohsiung 80708, Taiwan.
authors.forename: Chien-Chiao
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, 100 Shih-Chuan first Road, Kaohsiung 80708, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chuang
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan First Road, Kaohsiung 80708, Taiwan.
authors.forename: Yeng-Tseng
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, 100 Shih-Chuan First Road, Kaohsiung 80708, Taiwan.|Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan first Road, Kaohsiung 80708, Taiwan.
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 11529, Taiwan.
authors.forename: Steve R
authors.initials: SR
authors.lastname: Roffler
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.|Ph.D. Program for Clinical Drug Discovery from Botanical Herbs, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
authors.forename: Kuo-Hsiang
authors.initials: KH
authors.lastname: Chuang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan first Road, Kaohsiung 80708, Taiwan.|Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, 100 Shih-Chuan First Road, Kaohsiung 80708, Taiwan.|Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, 100 Shih-Chuan First Road, Kaohsiung 80708, Taiwan.
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D019921:Biotinylation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000032:analysis* / Q000737:chemistry; D045663:Quantum Dots; D044967:Serum / Q000737:chemistry*
chemical_list: D000906:Antibodies; D011092:Polyethylene Glycols