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

• Published in: Drug delivery Vol. 25; no. 1; pp. 1066 - 1079
• Main Authors: Su, Chia-Yu, Chen, Michael, Chen, Ling-Chun, Ho, Yuan-Soon, Ho, Hsiu-O, Lin, Shyr-Yi, Chuang, Kuo-Hsiang, Sheu, Ming-Thau
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.11.2018; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: active targeting; Antigens; Bispecific antibody; Cancer therapies; chemotherapeutics; docetaxel; Drug delivery systems; Drugs; Epidermal growth factor; Immunoglobulins; Ligands; Lipids; Medicine; mPEGylated nanocarriers; Nanoparticles; Pharmacy; Polyethylene glycol; Tumors; Bispecific antibody; docetaxel; active targeting; chemotherapeutics; mPEGylated nanocarriers
• ISSN: 1071-7544; 1521-0464; 1521-0464
• DOI: 10.1080/10717544.2018.1466936

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 (L sb MDDs) were endowed with active targetability to improve the chemotherapeutic efficacy of DTX. DTX-loaded mPEGylated L sb MDDs 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 L sb MDDs to form BsAbs-L sb MDDs formulations, respectively, referred as the DNS-L sb MDDs and HER2-L sb MDDs. Results demonstrated that the physical characteristics of the BsAbs-L sb MDDs were similar to those of the plain L sb MDDs but more slowly released DTX than that from the L sb MDDs. Results also showed that the HER2-L sb MDDs 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-L sb MDDs preserved the physical properties of the L sb MDDs and actively targeted tumors with a drug cargo to enhance drug accumulation in tumors leading to greater antitumor activity against antigen-positive tumors.