title: One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles.
abstract: Methoxy PEGylated nanoparticles (mPEG-NPs) are increasingly used for cancer imaging and therapy. Here we describe a general and simple approach to confer tumor tropism to any mPEG-NP. We demonstrate this approach with humanized bispecific antibodies (BsAbs) that can bind to both mPEG molecules on mPEG-NPs and to EGFR or HER2 molecules overexpressed on the surface of cancer cells. Simple mixing of BsAbs with mPEG-NPs can mediate preferential binding of diverse mPEG-NPs to cancer cells that overexpress EGFR or HER2 under physiological conditions and significantly increase cancer cell killing by liposomal doxorubicin to EGFR(+) and HER2(+) cancer cells. BsAbs modification also enhanced accumulation of fluorescence-labeled NPs and significantly increased the anticancer activity of drug-loaded NPs to antigen-positive human tumors in a mouse model. Anti-mPEG BsAbs offer a simple one-step method to confer tumor specificity to mPEG-NPs for enhanced tumor accumulation and improved therapeutic efficacy.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Chien-Han
authors.initials: CH
authors.lastname: Kao
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Kuo-Hsiang
authors.initials: KH
authors.lastname: Chuang
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chuang
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Ta-Chun
authors.initials: TC
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Yuan-Chin
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: Taiwan Liposome Company, Ltd., Taipei 11503, Taiwan.
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Tseng
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Bing-Mae
authors.initials: BM
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan. Electronic address: sroff@ibms.sinica.edu.tw.
authors.forename: Steve R
authors.initials: SR
authors.lastname: Roffler
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: tlcheng@kmu.edu.tw.
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D018033:Antibodies, Bispecific / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry; D041702:BALB 3T3 Cells; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D061848:Optical Imaging; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
chemical_list: D000903:Antibiotics, Antineoplastic; D018033:Antibodies, Bispecific; D061067:Antibodies, Monoclonal, Humanized; D004317:Doxorubicin; D004337:Drug Carriers; D066246:ErbB Receptors; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; C506643:liposomal doxorubicin; C028210:monomethoxypolyethylene glycol
keywords: Bispecific antibody; Cancer imaging; Methoxy poly(ethylene glycol); PEGylated nanoparticle; Targeted therapy