Title: Herceptin-functionalized tamoxifen-loaded albumin nanoparticles for enhanced delivery to HER2-positive breast cancer cells

Biography:

Seyed Abbas Shojaosadati got his Ph.D. from Birmingham University in 1988 and is a distinguished professor of TMU who has his expertise in industrial biotechnology, recombinant protein production and nanobiotechnology. A research group has been developed under his supervision for more than a decade to synthesize and modify various nanoparticles for targeted drug delivery with outstanding published articles. Currently, his research group works collaboratively with other nanotechnological laboratories to develop the capacity for future studies.

Abstract

Statement of the Problem: Breast cancer is a one of the main cause of death worldwide. Chemotherapeutic drugs are used as the frontline treatment of breast and other epithelial malignancies. They can be effective solely or in combination with other therapeutic agents [1]. Tamoxifen (TMX) belongs to a class of non-steroidal triphenylethylene derivatives, and is the first selective estrogen receptor modulator[2]. Herceptin has been widely used for treating breast cancer due to overexpression of human epidermal growth factor receptor-2 (HER2) by cells. Combination of TMX with Herceptin can promotes the therapeutic effectiveness of the anti-cancer delivery system. The role of HER2 in the pathogenesis of breast cancer has been well reported [3].

Human serum albumin (HSA) proved to be a promising carrier for targeted drug delivery to tumor cells, as so many therapeutic agents can be encapsulated within HSA[4]. The coupling of the antibody Herceptin to TMX-HSA nanoparticles takes advantage of the capability of HER2-positive cells to incorporate substances binding to HER2. In our present study, we developed TMX-loaded-HSA nanoparticles with desolvation and NAB-technology which were covalently modified on their surface with thiolated Herceptin with special focus on the effectiveness of antibody conjugation. The goal of this study was to show the efficacy of a nanoparticle albumin bound drug delivery system in comparison with an analogue albumin-based nanoparticles’ active targeting with Herceptin conjugation. For this purpose, four different delivery system were investigated based on their biological activity by cell culture. First, tamoxifen-loaded albumin nanoparticles via high pressure homogenizer, as a model containing unchanged albumin secondary structure; second, the tamoxifen-loaded nanoparticles via desolvation method as a model with dramatically changed albumin structure; and finally, the Herceptin-conjugated nanoparticles prepared by these two.