Optimization of aptamer-based manganese doped zinc sulphide/chitosan and carbon dots/chitosan as drug nanocarriers for controlled release of Mitomycin C

Drug delivery system (DDS) using nanocarriers have gained immense acclamation as a new prospect in nanomedicine. Conventional free drug delivery is associated with low therapeutic windows and inadequate therapeutic efficiency. Nanocarriers is outlined as a platform to combat such hurdles by transporting and releasing the drug precisely at the target site with maximum efficiency and safety in controlled manner. Therefore, in the present work, DDS based on hybrid two types of quantum dots (QDs); manganese doped zinc sulphide (Mn:ZnS) and carbon dots (CDs); incorporated onto chitosan (CS) as drug nanocarriers for Mitomycin C (MMC), further conjugated with aminated aptamer (Apt02); MMC@Mn:ZnS/CS-Apt02 and MMC@CDs/CS-Apt02 have been successfully synthesized. The physicochemical characterizations of nanocarriers were assessed using fieldemission scanning electron microscopy (FESEM), High Resolution Transmission Electron Microscopy (HRTEM), and Fourier Transform Infrared Spectroscopy (FTIR). The morphological analysis shows that both DDS exhibited nearly spherical shape with average particle size ranging from 80 to 110 nm. Subsequently, FTIR results reveals that there is slight shifting in absorbance peak at 1646cm-1 in both DDS due to the formation of hydrogen bond between amide group in MMC with hydroxyl group in chitosan. The drug encapsulation efficiency and drug release studies were further evaluated using UV-Vis Spectroscopy at 362 nm. The highest encapsulation efficiency were obtained as 82.6 ± 2.2% and 83.7 ± 0.7% for MMC@Mn:ZnS-CS and MMC@CDs-CS, respectively. The cumulative drug release percentages at pH 5.5 were 82.86 ± 1.33, and 81.44 ± 2.41 for MMC@CDs-CS-Apt02, and MMC@Mn:ZnS-CS-Apt02, respectively. Preliminarily, the binding affinity of two sequences of aptamers, Apt01 and Apt02 towards Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) have been assessed. From molecular docking and experimental analyses, Apt02 exhibit better binding affinity towards the VEGFR1. Hence, Apt02 has been used for the conjugation with TDDS. Finally, the interaction of DDS towards synthetic VEGFR1 were evaluated using fluorescence spectroscopy. An intense emission peak centered at 610 nm and 430 were observed for MMC@Mn:ZnS/CS-Apt02- VEGFR1 and MMC@CDs/CS-Apt02-VEGFR1, respectively. These DDS were used in proof-of-concept studies as a possible application in targeted drug delivery application.

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