Mitochondrial dysfunction mediated apoptosis of HT-29 cells through CS-PAC-AgNPs and investigation of genotoxic effects in zebra (Danio rerio) fish model for drug delivery

Abstract

The present study reports the validation of cancer nanotherapy using proanthocyanidin (PAC). Nowadays, in vitro and in vivo deliveries of nanoparticle (NPs) drugs have been paid more attention, intensively. Moreover, the current chemotherapeutic drugs have few first rate drawbacks including lack of specificity and requirement of excessive drug doses. To overcome this problem of chemotherapy, the attainment of high drug loading in combination with degradable polymer nanoparticles (for instance,chitosan) is a trending research in cancer biology. Hence, in this study, the synthesized PAC-AgNPs were successfully crosslinked with chitosan nanoparticles (CS-PAC-AgNPs), which were found to be spherical or polygonal in shape with a median size of 70.68 nm and 52.16 nm as observed by FTIR, FESEM and TEM analysis; thus, being suitable for drug delivery. CS-PAC-AgNPs were taken up via endocytosis by cancer cells and enabled the release cytochrome-C from mitochondria, followed by dysregulation of anti-apoptotic protein Bcl2 family, inducing the apoptotic mediated activation of caspase 9 and 3. To identify the genotoxicity of the synthesized CS-PAC-AgNPs, the mortality, hatching rate, malformation and abnormalities of embryo/larvae of the vertebrate zebra fish model ( Danio rerio ) were observed in a dose-time-dependent manner. This improved cancer nanotherapy can thus be utilized as a novel nanocombination for inducing apoptosis in vitro and in vivo .

Insights into Shape-Based Silver Nanoparticles: A Weapon to Cope with Pathogenic Attacks

“…Nowadays, extensive use of antibiotics and the evolution of antibiotic resistance in pathogens have reached an alarming stage. To face this scenario, Ag 0 in the form of NPs or a combination with classical antibiotics has made a remarkable comeback with the potential antibacterial formulation in the medicinal and healthcare field. , Apart from their antibacterial activity, AgNPs have shown their potential against broad-spectrum microbes (fungus and virus) and insects. − Owing to these unique attributes, AgNPs are being used in various fields such as textile industries, food packaging, cosmetic industry, catalysis, sensors, various bioapplications, coatings, plasmonic, optoelectronics, DNA sequencing, SERS, climate change, contamination control, tranquilizer conveyance agents, farming, electronic devices, inks, adhesives, and pastes. − Some special applications of AgNPs are schematically presented in Figure .…”

Ultra-Small Iron Nanoparticles Target Mitochondria Inducing Autophagy, Acting on Mitochondrial DNA and Reducing Respiration

“…This work addresses, for the first time, a comprehensive study about the traffic of iron and other elements in the subcellular fractions, the integrity of the mtDNA, the mitochondrial functionality and the induction of the autophagy process that will increase the knowledge about the metabolism of nanoparticles and its possible application in therapy focused on mitochondria. To perform the study HT-29 cell line was chosen based on previous studies in which the implications of nanomaterials in therapy have been evaluated [ 13 , 14 , 15 ].…”

Marine Compounds, Mitochondria, and Malignancy: A Therapeutic Nexus

“…CS-PAC-AgNPs can activate the release of cyt. c, induce the activation of caspase-9 and caspase-3, inhibit cancerous cellular proliferation, and suppress the formation of antiapoptotic proteins in HT-29 cells [ 74 ]. Lycopene, a tetraterpene present in tomatoes and several foods, is the most abundant carotenoid accumulating in prostate tissues and has been found to have antineoplastic properties in prostate cancer.…”