One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles

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

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25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9930-9940
Number of pages11
JournalBiomaterials
Volume35
Issue number37
DOIs
Publication statusPublished - Dec 1 2014

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Keywords

  • Bispecific antibody
  • Cancer imaging
  • Methoxy poly(ethylene glycol)
  • PEGylated nanoparticle
  • Targeted therapy

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics
  • Medicine(all)

Cite this

Kao, C. H., Wang, J. Y., Chuang, K. H., Chuang, C. H., Cheng, T. C., Hsieh, Y. C., Tseng, Y. L., Chen, B. M., Roffler, S. R., & Cheng, T. L. (2014). One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles. Biomaterials, 35(37), 9930-9940. https://doi.org/10.1016/j.biomaterials.2014.08.032