Research Article: Synthesis, cytotoxicity and antitumour mechanism investigations of polyoxometalate doped silica nanospheres on breast cancer MCF-7 cells

Date Published: July 13, 2017

Publisher: Public Library of Science

Author(s): Hongqian Cao, Chunyan Li, Wen Qi, Xiangjun Meng, Rui Tian, Yanfei Qi, Wei Yang, Juan Li, Jamshidkhan Chamani.

http://doi.org/10.1371/journal.pone.0181018

Abstract

Polyoxometalates (POMs) have shown the potential anti-bacterial, anti-viral and anti-tumor activities. In order to improve their physiological stability and antitumour activity for medical application, K2Na[AsIIIMo6O21(O2CCH2NH3)3]·6H2O doped silica nanospheres (POM@SiO2) with diameters of ~40 nm have been synthesized by the water-in-oil microemulsion method in this study. The obtained spheres were morphologically uniform nanosized and nearly monodispersed in solution. The nanoparticles had high entrapment efficiency, which was upto 46.2% by the inductively coupled plasma mass spectrometry (ICP-MS) analysis and POMs slowly released from the nanospheres both in the PH 7.4 and 5.5 phosphate buffer saline (PBS) solutions in 60 h. The in vitro MTT assays of particles on MCF-7 cell line (a human breast adenocarcinoma cell line) exhibited enhanced antitumor activity compared to that of plain polyoxometalate. The IC50 value of the POM@SiO2 nanoparticles was 40.0 μg/mL at 24 h calculated by the encapsulated POM concentration, which was much lower comparing to that of 2.0 × 104 μg/mL according to the pure POM. And the SiO2 shells showed low inhibitory effect at the corresponding concentration. Confocal images further indicated the cell morphology changes and necrosis. Flow cytometric analysis showed nanoparticles induced the apoptosis by arresting the cells in S phase and western blot analysis indicated they promoted apoptosis by inhibiting the Bcl-2 protein. Moreover, the study of interactions between human serum albumin (HSA) and the nanoparticles indicated the fluorescence quenching was static, and the nanoparticles were likely to bind to HSA and changed its conformation.

Partial Text

Cancer is a serious public health problem which threatens human health in the world due to the increasing incidence and mortality. And breast cancer is one of the most common types among other malignancies in women, along with a major cause of mortality worldwide. New cases of breast cancer diagnosed in 2015 accounted for approximately 12% of all new malignancy cases and the mortality accounted for 25% of all cancer cases in women. The United Kingdom had the highest incidence among the top seven countries. Breast cancer undergoes uncontrolled growth and metastasizes to distance sites, such as brain, liver and bone [1]. The worldwide new cases of female breast cancer is estimated to reach nearly 3.2 million per year by 2050 [2]. The incidence increases with age and more than half of cases are 65 years or older [3]. In spite of treatment, >4,000 patients succumbed to the malignancy in the US in 2016 [4]. Despite intensive investigation of breast cancer cell lines, the cellular and molecular mechanisms between MCF-7 cell line and the drug polyoxometalate (POM) are still limited. In the cancer treatment, chemotherapeutic is a key method during the illness of patients. Some skin peptides obtained from amphibians even have also been demonstrated possessing the anticancer effects [5]. Because of its significance, there has been long standing interest in the development of novel approaches to improve the therapeutic index of chemotherapy.

In summary, we report the in vitro anti-proliferative effects on MCF-7 cells of the POM@SiO2 nanoparticles with small size around 40 nm. The nanoparticles significantly enhanced the cytotoxicity on the cells comparing to that of the pure POM. SiO2 shells controlled the release efficiency as the drug delivery system. The higher antitumor activity could be due to their higher cellular penetration for the small size and surface modification by the shells. The Flow cytometry analysis results showed that the nanoparticles could induce apoptosis and cell cycle S phase arrest. The HSA binding experiment showed that the complex changed the conformation and quenched the fluorescence of the protein, which belonged to a static quenching. Furthermore, the antitumour effect of other cell lines and modification with target molecules on the spheres should be further investigated.

 

Source:

http://doi.org/10.1371/journal.pone.0181018

 

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