Doxorubicin-Conjugated Terbium-Doped Carbon Dots for Site-Specific Colon Cancer Theranostics
Dhanavardhini Kalyanasundaram, P. Sagayaraj, Tiasha Dasgupta, G.R. Tharani, Ramasamy Tamizhselvi, Anandh Sundaramoorthy, Nireekshana Nandigam, Udayakumar Kanniyappan, Venkat S. Kumar, S. Karthikeyan, Shanmugavel Chinnathambi, Ganesh N. Pandian, Andrews Nirmala Grace, Casimeer C. Sangeetha, Rajendiran Mangaiyarkarasi
Abstract
This work focuses on synthesizing fluorescent rare earth terbium-doped carbon dots (CD-Tb) as a nanodrug carrier for doxorubicin (DOX) drug moieties using the hydrothermal method. The nature of CD-Tb nanoparticles in the absence and presence of DOX was evaluated using various spectroscopic and microscopic techniques, namely, X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), Zeta potential analyzer, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), UV–visible, fluorescence emission, and lifetime spectroscopy. The synthesized CD-Tb nanoparticles were found to be approximately 7 nm in size and spherical, with a surface charge of −20.7 mV. They are biocompatible with electron-rich amino groups on their surface and are used for the bioconjugation of DOX, an anticancer drug. The photophysical characterization shows 92.5% of adsorption and 89% of in vitro release of DOX from CD-Tb nanoparticles. This might be due to the presence of carboxyl and amino groups on the DOX surface and CD-Tb nanoparticles. The effective concentration of CD-Tb nanoparticles and DOX was achieved at a stoichiometric ratio of 1:1.5. Further, the Stern–Volmer quenching rate constant ( K q ) of CD-Tb-DOX was calculated as 4.9 × 10 10 L/mol·s –1, and the binding of nanoparticles with various concentrations of DOX is found to be static. In addition, the in vitro antitumoral activity of free DOX and the CD-Tb-DOX against Caco-2 cancer cell lines (human colon cancer) and L929 cell lines (mouse fibroblast cells) was evaluated as the healthy cell model. CD-Tb-DOX’s in vitro cytotoxic evaluation result shows higher cytotoxicity and morphological changes at Caco-2 colon cancer tumor sites than free DOX. In brief, this study confirms that the synthesized CD-Tb-DOX nanocarriers could significantly enhance the metabolic damage in the Caco-2 cancer cell lines (human colon cancer) and facilitate the action of cellular apoptosis, which might be helpful in site-specific targeting drug delivery applications.