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: Chien-Han Kao, Jaw-Yuan Wang, Kuo-Hsiang Chuang, Chih-Hung Chuang, Ta-Chun Cheng, Yuan-Chin Hsieh, Yun-Long Tseng, Bing-Mae Chen, Steve R Roffler, Tian-Lu Cheng
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 37 Pg. 9930-9940 (Dec 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 25212525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Antibodies, Bispecific
• Antibodies, Monoclonal, Humanized
• Drug Carriers
• liposomal doxorubicin
• Polyethylene Glycols
• Doxorubicin
• monomethoxypolyethylene glycol
• ErbB Receptors
• Receptor, ErbB-2

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, therapeutic use)
• Antibodies, Bispecific (chemistry)
• Antibodies, Monoclonal, Humanized (chemistry)
• BALB 3T3 Cells
• Cell Line, Tumor
• Doxorubicin (administration & dosage, analogs & derivatives, therapeutic use)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• ErbB Receptors (analysis)
• Female
• Humans
• Magnetic Resonance Imaging
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (chemistry)
• Neoplasms (diagnosis, drug therapy)
• Optical Imaging
• Polyethylene Glycols (administration & dosage, chemistry, therapeutic use)
• Receptor, ErbB-2 (analysis)