2. Academic Validation
  3. 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

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

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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