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.