Glucose-conjugated glutenin nanoparticles for selective targeting and delivery of camptothecin into breast cancer cells.

Receptor-mediated drug delivery systems are a promising tool for targeting malignant cells to suppress/inhibit the malignancy without disturbing healthy cells. Protein-based nanocarrier systems possess numerous advantages for the delivery of variety of chemotherapeutics, including therapeutic peptides and genes. In the present work, glucose-conjugated camptothecin-loaded glutenin nanoparticles (Glu-CPT-glutenin NPs) were fabricated to deliver camptothecin to MCF-7 cells via GLUT-1 transporter protein. Initially, Glu-conjugated glutenin polymer was successfully synthesized through reductive amination reaction, and this was confirmed by FTIR and 13C-NMR. Then, camptothecin (CPT) was loaded into Glu-conjugated glutenin polymer forming Glu-CPT-glutenin NPs. The nanoparticles were studied for their drug releasing capacity, morphological shape, size, physical nature, and zeta potential. The fabricated Glu-CPT-glutenin NPs were found to be spherical in shape and amorphous in nature with 200-nm size range and a zeta potential of - 30 mV. Furthermore, MTT assay using Glu-CPT-glutenin NPs confirmed concentration-dependent cytotoxicity against MCF-7 cells after 24-h treatment, and IC50 was found to be 18.23 µg mL-1. In vitro cellular uptake study demonstrated that the Glu-CPT-glutenin NPs had enhanced endocytosis and delivered CPT in MCF-7 cells. A typical apoptotic morphological change of condensed nuclei and distorted membrane bodies was found after treatment with IC50 concentration of NPs. The released CPT from NPs also targeted mitochondria of MCF-7 cells, significantly increasing the level of reactive oxygen species and causing the damage of mitochondrial membrane integrity. These outcomes confirmed that the wheat glutenin can positively serve as a significant delivery vehicle and enhance the anticancer potential of this drug.

Graph theoretical network analysis, in silico exploration, and validation of bioactive compounds from Cynodon dactylon as potential neuroprotective agents against α-synuclein.

Introduction: Parkinson's disease (PD) is a chronic, devastating neurodegenerative disorder marked by the death of dopaminergic neurons in the midbrain's substantia nigra pars compacta (Snpc). In alpha-synuclein (α-Syn) self-aggregation, the existence of intracytoplasmic inclusion bodies called Lewy bodies (LBs) and Lewy neurites (LNs) causes PD, which is a cause of neuronal death. Methods: The present study is aimed at finding potential bioactive compounds from Cynodon dectylon that can degrade α-Syn aggregation in the brain, through in silico molecular docking investigations. Graph theoretical network analysis was used to identify the bioactive compounds that target α-Syn and decipher their network as a graph. From the data repository, twenty-nine bioactive chemicals from C. dactylon were chosen and their structures were retrieved from Pubchem. On the basis of their docking scores and binding energies, significant compounds were chosen for future investigation. The in silico prediction of chosen compounds, and their pharmacokinetic and physicochemical parameters were utilized to confirm their drug-likeness profile. Results: During molecular docking investigation the bioactive compounds vitexin (-7.3 kcal.mol-1) and homoorientin (-7.1 kcal.mol-1) showed significant binding energy against the α-Syn target protein. A computer investigation of molecular dynamics simulation study verifies the stability of the α-Syn-ligand complex. The intermolecular interactions assessed by the dynamic conditions indicate that the bioactive compound vitexin has the potency to prevent α-Syn aggregation. Conclusion: Interestingly, the observed results indicate that vitexin is a potential lead compound against α-Syn aggregation, and in vitro and in vivo studies are warranted to confirm the promising therapeutic capability.