Nanochemopreventive effect of polymer functionalized gold nanoparticles containing hesperetin drug inhibited proliferation and induced apoptosis in Hep3B cells

To investigate the potential biomedical applications of Polymer functionalized gold nano particles for predictive, preventive and personalised nanomedicine in liver cancer. The present study is designed to evaluate the nanochemopreventive effect of hesperetin conjugated gold nanoparticles (Au-mPEG(5000)-S-HP) involved in proliferation and induced apoptosis in Hep3B cells. We have previously reported that well synthesized and characterized 220 nm in size of Au-mPEG(5000)-S-HP NPs and pure hesperetin at different dose (10 µg/ml-250 µg/ml) on Hep3B cells for 48 h by MTT assay. Pure hesperetin and Hesperetin loaded gold nanoparticles (Au-mPEG (5000)-S-HP NPs) were inhibited the growth of Hep3B cells in a dose dependent manner. The IC50 value of pure hesperetin is 63.18 μg/ml and the IC50 value of when compare with Au-mPEG(5000)-S-HP NPs is 44.3 μg/ml. The classified apoptotic and non-apoptotic cells were identified in PI staining and EB/AO staining. Immunoblotting results showed that the protein expression of cell cycle checkpoint protein p53 and pro-apoptotic protein Bax, Cyt-c and caspase-3 were up-regulated while the matrix metalloproteinases MMPs 2/9, inflammatory and proliferative markers NF-kB, PCNA and Cyclin D1 was down-regulated and the anti-apoptotic protein Bcl-2 and Survivin significantly increase the expression in hesperetin conjugated gold nanoparticles treated cells. Moreover our data demonstrated that Au-mPEG(5000)-S-HP nanoparticles treated inhibit proliferation and induced apoptosis in human liver cells. Treatment of hesperetin conjugated gold (Au-mPEG(5000)-S-HP) nanoparticles increase the proportion of cells with reduced DNA content (sub G0-G1 peak) indicative of apoptosis with loss of cells in the G1 phase.