Bispecific antibodies (anti-mPEG/anti-HER2) for active tumor targeting of docetaxel (DTX)-loaded mPEGylated nanocarriers to enhance the chemotherapeutic efficacy of HER2-overexpressing tumors

  • Drug Deliv. 2018 Nov;25(1):1066-1079. doi: 10.1080/10717544.2018.1466936.
Chia-Yu Su  1 ,  Michael Chen  2 ,  Ling-Chun Chen  3 ,  Yuan-Soon Ho  4 ,  Hsiu-O Ho  1 ,  Shyr-Yi Lin  5  6  7 ,  Kuo-Hsiang Chuang  2  8 ,  Ming-Thau Sheu  1
Affiliations
  • 1. a School of Pharmacy, College of Pharmacy , Taipei Medical University , Taipei , Taiwan, ROC.
  • 2. b Ph.D. Program in Clinical Drug Development of Chinese Herbal Medicine , Taipei Medical University , Taipei , Taiwan, ROC.
  • 3. c Department of Biotechnology and Pharmaceutical Technology , Yuanpei University of Medical Technology , Hsinchu , Taiwan, ROC.
  • 4. d Graduate Institute of Medical Sciences, College of Medical Science and Technology , Taipei Medical University , Taipei , Taiwan, ROC.
  • 5. e Department of Primary Care Medicine , Taipei Medical University Hospital , Taipei , Taiwan, ROC.
  • 6. f Department of General Medicine, School of Medicine, College of Medicine , Taipei Medical University , Taipei , Taiwan, ROC.
  • 7. g TMU Research Center of Cancer Translational Medicine , Taipei Medical University , Taipei , Taiwan, ROC.
  • 8. h Graduate Institute of Pharmacognosy , Taipei Medical University , Taipei , Taiwan, ROC.
PMID: 29718725 DOI: 10.1080/10717544.2018.1466936
Abstract

Anti-mPEG/anti-human epidermal growth factor receptor 2 (HER2) bispecific antibodies (BsAbs) non-covalently bound to a docetaxel (DTX)-loaded mPEGylated lecithin-stabilized micellar drug delivery system (LsbMDDs) were endowed with active targetability to improve the chemotherapeutic efficacy of DTX. DTX-loaded mPEGylated LsbMDDs formulations were prepared using lecithin/DSPE-PEG(2K or 5K) nanosuspensions to hydrate the thin film, and then they were subjected to ultrasonication. Two BsAbs (anti-mPEG/anti-DNS or anti-HER2) were simply mixed with the LsbMDDs to form BsAbs-LsbMDDs formulations, respectively, referred as the DNS-LsbMDDs and HER2-LsbMDDs. Results demonstrated that the physical characteristics of the BsAbs-LsbMDDs were similar to those of the plain LsbMDDs but more slowly released DTX than that from the LsbMDDs. Results also showed that the HER2-LsbMDDs suppressed the growth of HER2-expressing MCF-7/HER2 tumors, increasing the amount taken up via an endocytosis pathway leading to high drug accumulation and longer retention in the tumor. In conclusion, the BsAbs-LsbMDDs preserved the physical properties of the LsbMDDs and actively targeted tumors with a drug cargo to enhance drug accumulation in tumors leading to greater antitumor activity against antigen-positive tumors.

Keywords
Bispecific antibody; active targeting; chemotherapeutics; docetaxel; mPEGylated nanocarriers.
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