Gold nanoparticles-based targeted delivery of rapamycin and Olaparib to breast cancer: An in vitro and in vivo approach

Triple negative form of breast cancer (abbreviated as TNBC) is considered as the most aggressive form causing high mortality worldwide. Different treatment modalities such as chemotherapy, surgery, hormonal therapy and radiation therapy are employed for eliminating breast cancer, which are associated with many limitations. Therefore, considering the significance of metal nanoparticles in the biomedical sector, especially gold nanoparticles, in the current manuscript, we have designed and developed a combinatorial approach for synthesizing two types of gold (Au) nanoformulations (Au-Dex-MUA-Rapa, Au-Dex-MUA-Ola) using 11-mercaptoundecanoic acid (MUA), dexamethasone (Dex) (glucocorticoid receptor targeted molecule) along with rapamycin (Rapa: inhibitor of mTOR) or olaparib (Ola: inhibitor of PARP) against TNBC. These gold nanoformulations were characterized thoroughly using several analytical techniques such as TEM, spectroscopy, DLS, HPLC and ICPOES. The in vitro MTT assays (normal cells: HEK-293 and CHO) and ex vivo CAM assay displays the biocompatible properties of the conjugated gold nanoformulations. Further, the anticancer properties of the conjugated gold nanoformulations in TNBC cells (MDA-MB-231) were evaluated through several in vitro experiments along with plausible mechanism of action. The intraperitoneal administration of gold nanoformulations into the breast tumor bearing BALB/c mice inhibits the tumor growth and increases their survivability. Additionally, we have investigated the plausible mechanistic studies behind the anticancer properties of the conjugated gold nanoformulations. Finally, we have found the non-toxic nature of these nanoformulations at therapeutic dose. Considering the above results, the conjugated gold nanoformulations could be used as an alternative therapeutic strategy for the treatment of breast carcinoma in near future.