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.
a Department of Pharmacology , J.S.S. College of Pharmacy (off-Campus), J.S.S. University , Mysore , India.
Shashank
S
Tummala
a Department of Pharmacology , J.S.S. College of Pharmacy (off-Campus), J.S.S. University , Mysore , India.
M N Satish
MN
Kumar
a Department of Pharmacology , J.S.S. College of Pharmacy (off-Campus), J.S.S. University , Mysore , India.
Sai Kiran
SK
Pindiprolu
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006046:Gold / Q000737:chemistry*; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology*; D000077150:Oxaliplatin; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000906:Antibodies; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; D000077150:Oxaliplatin; D006046:Gold
Colorectal cancer; DR5; TRAIL; oxaliplatin; site specific