Cell-nucleus Targeted Peptide Tethered Quadruple Carbon Dots for Treatment of High-grade Gliomas

Abstract

Ultimate goal of the nanomedicine is built on the idea of robust targeted delivery of complex assemblies that contain sufficient amount of multiple therapeutics and diagnostic agents for highly localized payload release with no adverse side effects. Besides the numerous efforts on the field of cancer specific nanomedicine, still there is a great need for improvements in terms of target specificity. Previously, we have reported a target-specific carbon dots- based dual nano-drug delivery system. In study, for the first time in literature, surface functional group of the carbon dots were conjugated with four different ligands namely, two peptides (shPep-1 and lnPep-1) and two chemotherapeutic drugs (epirubicin and temozolomide). Here, we advanced our drug delivery system as a dual drug nano-carrier (quadruple nano-model) that explicitly targets the IL-13Rα2 receptors and the nucleus of high-grade glioma brain tumors. The successful conjugation of each molecule onto carbon dots (CDs) was meticulously characterized with numerous analytical techniques. Additionally, the in vitro cell viability assay revealed that quadrupole nano-model significantly reduced the cancer cell viability compared to the single peptide dual drug linked conjugates. Further, in vitro bioimaging studies using FITC conjugated single and dual peptides models, showed that dual peptide model exhibited greater FITC fluorescence throughout the cell including the nucleus compared to the single peptide models. This observation is evidence for improved cancer cell uptake and nucleus colocalization of quadrupole nano-model. Our quadrupole nano-model fully serves the ultimate goal of nanomedicine as a nanocarrier which contains two targeting peptides and two therapeutics simultaneously.

Carbon-Based Nanoparticles and Their Surface-Modified Counterparts as MALDI Matrices

“…As mentioned before, functionalization of CDs is a facile task due to the pre-existing functional groups on the CD surface. − Not only can these functional groups contribute to charge transfer during ionization, but they can also help with the solubilization of the analytes by forming polar and nonpolar intermolecular interactions with the analytes during sample preparation, leading to a uniformly dispersed mixture of molecules. , CDs with −NH 2 and −COOH functional groups were synthesized to serve as MALDI matrices for the detection of cholesterol . Computational evaluation of cholesterol interaction with CDs showed that, upon ionization and desorption, the interaction between the carboxylic acid group of CDs and cholesterol was responsible for electron transfer and subsequent loss of a water molecule followed by capturing a proton (Figure ); cholesterol was detected as [M-H 2 O+H] + ionic species (Figure ).…”