Abstract
Polo-like kinase 1 (PLK-1) is a protein kinase that plays a significant role in the initiation, maintenance, and completion of mitotic processes in the cell cycle. PLK-1 has been recorded to be over-expressed in various human cancers and is associated with poor prediction; thus it is an attractive target for anticancer therapy. Novel alpha-santalol functionalized chitosan nanoparticles were synthesized using the sol gel method and were assessed for their in vitro (MTT, apoptotic staining assays, and cell cycle analysis) and in vivo activities. alpha-Santalol loaded chitosan NPs inhibited the proliferation of triple negative breast cancer (MDA-MB-231) at an inhibitory concentration of (IC50) about 4.5 mu g mL; meanwhile, in normal cells, no adverse effects were exhibited up to 100 mu g mL(-1). The findings also implicated a decreased expression of the anti-apoptotic protein, BCL-2 with PLK-1 and an increase in the expression of BAD, caspases and BAX. However, in in vivo studies, the treated animal group exhibited no aberrant effects in vital organs or blood parameters. Tumor growth was significantly inhibited after i.v. injection of alpha-santalol loaded chitosan NPs at a dose of 5 mg kg(-1). Taken together, the alpha-santalol functionalized chitosan NPs hold great potential in biomedical applications, especially cancer theranostics, due to their versatile nature as well as diagnostics for clinical tumor biology.
NSTL
Royal Soc Chemistry