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

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.

Enhanced drug internalization and therapeutic efficacy of PEGylated nanoparticles by one-step formulation with anti-mPEG bispecific antibody in intrinsic drug-resistant breast cancer

“…Thus, the BsAb can be modified on diverse mPEG-based materials, such as liposome, Qdot, FeOdot and AuNP 33 and micelle. 38 In addition, by designing a panel of BsAbs, a diverse set of PEG-NPs can be rapidly created to target different biomarkers (e.g., EGFR, 39,40 ICAM-1, 41 etc.) expressed in individual diseases for diagnosis and therapy.…”

Overcoming Hurdles in Nanoparticle Clinical Translation: The Influence of Experimental Design and Surface Modification

“…Perhaps one of the most elegant examples of the strategy can be found in the recent study of Su et al The investigative team targeted the HER2 receptor, known to be overexpressed in breast cancer cells, using PEGylated micelles encapsulating docetaxel. The micelles were further modified by tethering an anti-HER2 antibody to the surface of the micelle via an anti-mPEG linker [68]. This strategy yielded promising results in MCF7 breast cancer cells and demonstrated the power of using antibody targeting as a tool.…”

Fluorescence Guidance in Surgical Oncology: Challenges, Opportunities, and Translation

“…For instance, antibody drug conjugates are being utilized in both preclinical studies as well as early and late stage clinical trials. These studies have shown increased ability to target diseased cells, and increased antitumor potency [140][141][142][143]. Peptide and aptamer based delivery systems have also shown efficacy in reducing offtarget effects and increasing drug delivery to the tumor [144][145][146].…”