Frontiers in Molecular Biosciences (May 2021)
Theranostic Mesoporous Silica Nanoparticles Loaded With a Curcumin-Naphthoquinone Conjugate for Potential Cancer Intervention
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.
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