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 Delivery

Ling-Chun Chen¹  Shyr-Yi Lin²  Yuan-Soon Ho³  Michael Chen⁴  Kuo-Hsiang Chuang⁵  Hsiu-O Ho⁶  Chia-Yu Su⁶  Ming-Thau Sheu⁶ 

[1] Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan, ROC;Department of Primary Care Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC;Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC;TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan, ROC;Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC;Ph.D. Program in Clinical Drug Development of Chinese Herbal Medicine, Taipei Medical University, Taipei, Taiwan, ROC;Ph.D. Program in Clinical Drug Development of Chinese Herbal Medicine, Taipei Medical University, Taipei, Taiwan, ROC;Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan, RO;School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC;

关键词: Bispecific antibody;    docetaxel;    mPEGylated nanocarriers;    active targeting;    chemotherapeutics;   

DOI  :  10.1080/10717544.2018.1466936

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY