期刊
BIOMATERIALS
卷 35, 期 37, 页码 9930-9940出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.08.032
关键词
Bispecific antibody; Methoxy poly(ethylene glycol); PEGylated nanoparticle; Targeted therapy; Cancer imaging
资金
- National Research Program for Biopharmaceuticals, Ministry of Science and Technology, Taipei, Taiwan [MOST 103-2325-B-037-007, NSC102-2321-B-037-001]
- Ministry of Health and Welfare, Taiwan [MOHW103-TD-B-111-05]
- NSYSU-KMU Joint Research Project [NSYSUKMU103 I-003]
- Grant of Biosignature in Colorectal Cancers, Academia Sinica, Taiwan
- Academia Sinica Research Program on Nanoscience and Nanotechnology
- [KMU-DT103005]
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. (C) 2014 Elsevier Ltd. All rights reserved.
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