Improved anti-tumor activity of oxaliplatin by encapsulating in anti-DR5 targeted gold nanoparticles.
Oxaliplatin is one of the chemotherapeutic agents in the first line therapy for treatment of colorectal cancer. But, limitations of chemotherapy affects the clinical applicability of oxaliplatin depriving its activity at targeted site attributed to the lack of site specificity. This limitation paves the way for undesirable toxic effects to healthy cells resulting in sub-standard drug amount at the tumors obliging for increased dose. The present study emphasizes on formulating gold nanoparticles encapsulating oxaliplatin and later conjugating with anti-DR5 antibody for improved anti-cancer activity in a synergistic and site-specific manner. Oxaliplatin immuno-nanoparticles (Co-Ox-AuNPs) had shown sustained release and confirmed by fluorescence and flow cytometry studies. MTT assay exhibited 3-fold decrease in cell viability of nanoparticles comparable to oxaliplatin. Triple fluorescence method employed in HCT 116 and MCF-7 cells justified its site specificity. Annexin-propidium iodide (PI) and Acridine orange-ethidium bromide assays further supported the apoptotic activity. Moreover, caspase-dependent molecular mechanism behind oxaliplatin induced anti-cancer activity was explored by western blot analysis. Reduction in tumor size and volume in xenograft tumor models justified its in vitro activity. Oxaliplatin side effects were analyzed in mice and were confirmed for their clinical efficacy highlighting our formulation as an alternative to chemotherapy.
['Tummala|Shashank|S|', 'Kumar|M N Satish|MN|', 'Pindiprolu|Sai Kiran|SK|']
D000818:Animals D000906:Antibodies D000970:Antineoplastic Agents D000971:Antineoplastic Combined Chemotherapy Protocols D017209:Apoptosis D045744:Cell Line, Tumor D002470:Cell Survival D002626:Chemistry, Pharmaceutical D006046:Gold D045325:HCT116 Cells D006801:Humans D061986:MCF-7 Cells D008297:Male D053768:Metal Nanoparticles D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D009944:Organoplatinum Compounds D000077150:Oxaliplatin D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand D023041:Xenograft Model Antitumor Assays
oxaliplatin Colorectal cancer site specific DR5 TRAIL