Abstract 19P
Background
Polo-like kinase 1 (PLK1) is a protein kinase plays an important role in the initiation, maintenance, and completion of mitotic process. Human PLK1 has been shown to be over-expressed in a variety of human cancers, and elevated levels of PLK1 have been associated with poor prediction, leading to an attractive target for anticancer therapy.
Methods
A novel Silymarin functionalized FeO quantum cores (SiFeO QDs) were synthesized through one step synthesis method. For in vitro assay MTT, apoptotic staining assays and cell cycle analysis were performed. In vivo studies, xenocraft mice further administration of the SiFeO QDs at a dose of 25mg/kg body weight every other day for 14d. after 24h of the last treatment dose, the mice were left to monitor their survival or sacrificed to assess the antitumor activity.
Results
SiFeO QDs inhibited proliferation of Triple negative breast cancer cell lines, with mean inhibitory concentration of (IC50) value about 4.5µg/ml, meanwhile in non-dividing normal cells, it didn’t exhibit any adverse effects upto 50µg/ml. In animal models, administration of SiFeO QDs significantly inhibited the growth of MM2 breast cancer xenografts. It also accompanied by decreased expression of anti-apoptotic proteins, BCL-2, and MCL-1 and increased expression of BAX. Moreover, caspase-3 was activated to a greater extent after SiFeO QDs treatment. Impressively the treated group animal exihibit there is no aberrant effect in vital organs and blood parameters. Tumor growth was significantly inhibited after i.v. injection of SiFeO QDs at dose of 5mg/kg compared to free FeO QDs at dose of 25mg/kg. However, this system remarkably suppressed tumor growth in human breast cancer xenografts.
Conclusions
The significant antitumor efficacy of SiFeO QDs were attributed to the ability of the cores to show both prolonged blood circulation and high accumulation in tumors, as confirmed by near infrared (NIR) imaging systems. Taken all together, the SiFeO QDs hold great potential in biomedical applications especially cancer theranostics due to their versatile nature in therapy as well in diagnostics in clinical tumor biology.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Manickam Paulpandi.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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