Abstract
A novel theranostic molecule, derived from curcumin (Cur) and naphthoquinone (NQ), allowing for cancer targeting, detection and treatment was previously described and termed CurNQ. To allow for enhanced theranostic capabilities, advanced drug delivery techniques are required. To this end, mesoporous silica nanoparticles (MSN) were synthesized and CurNQ was loaded into its pores to form the novel nanosystem MSN_CurNQ. The formation of the nanosystem aimed to augment the drug delivery of CurNQ through the EPR effect and sustained release. Moreover, the loading of CurNQ into its pores, formed a fluorescent nanoparticle that can be tracked, detected and visualized. Herein, the synthesis of a novel nanosystem is described and its theranostic potential are explored in vitro. MSN with an average size of 108 d.nm, a zeta potential of −42 mV and a PDI of 0.150 were synthesized and were impregnated with CurNQ to form the novel nanosystem MSN_CurNQ. MSN_CurNQ was demonstrated to have pH-responsivity whereby after 96 h, at pH 7.4, 31.5% of CurNQ was released from the MSN compared to 57% release at pH 6.8, corresponding to an increase of 25.5% in release with a 0.6 pH drop. The innate fluorescence was then characterized through confocal and fluorescence microscopy. Microscopy images illustrated the distinct, high intensity innate fluorescence with a high background to target ratio, thus confirming detection capabilities and potentially extending MSN_CurNQ’s application to molecular imaging purposes. Moreover, the chemotherapeutic potential of MSN_CurNQ was demonstrated as cell viability was reduced to below 50% in OVCAR-5, CACO-2, CHLA, and MCF-7 cell lines. Furthermore, MSN_CurNQ displayed tumor specific toxicity whereby the cell viability was reduced to a far greater extent in the cancer cell lines compared to a healthy fibroblast cell line (p = 0.000). Indeed, the novel MSN_CurNQ nanosystem has potential for applications in cancer targeting, detection and treatment.
Highlights
Cancer is set to become the leading cause of death globally and is the biggest impediment to increased life expectancy in the 21st century as the global incidences and mortality rates are forever increasing (Bray et al, 2018)
Of nanoparticles were sonicated for 30 min at room temperature prior to analysis to reduce particle aggregation. 2 mL of the dispersed samples were filtered into disposable cuvettes and the size, polydispersity index (PDI) and zeta potential values were recorded at 25◦C on the ZetaSizer Nano ZS
The XRD scan of the synthesized MSN displayed a sharp peak confirming the presence of ordered pores owing to a regular periodic variation of the electron density in the mesoporous silica nanoparticles (Ciesla and Schuth, 1999)
Summary
Cancer is set to become the leading cause of death globally and is the biggest impediment to increased life expectancy in the 21st century as the global incidences and mortality rates are forever increasing (Bray et al, 2018). New and improved strategies for cancer diagnostics and targeted treatment is an immediate necessity. The search for new chemical entities for cancer treatment is ongoing. New cancer therapies should circumvent the issues that plague current chemotherapeutics, some of which include, high toxicity, non-specificity, cancer resistance and late diagnosis (Tran et al, 2017; Haider et al, 2020). One of the current trends in cancer research is the development of advanced platforms using nanotechnology that allows for simultaneous diagnostics and treatment, this field of research is referred to as theranostics (Saroj and Rajput, 2018). Concurrent diagnostics and treatment would allow for earlier detection and treatment of malignancy, resulting in improved prognosis and lower mortality rates (Wicki et al, 2015)
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