Improved anti-tumor activity of oxaliplatin by encapsulating in anti-DR5 targeted gold nanoparticles

Autor:	M N Satish Kumar, Shashank Tummala, Sai Kiran S.S. Pindiprolu
Rok vydání:	2016
Předmět:	Male Organoplatinum Compounds Cell Survival Colorectal cancer Chemistry Pharmaceutical medicine.medical_treatment Metal Nanoparticles Mice Nude Pharmaceutical Science Antineoplastic Agents Apoptosis 02 engineering and technology Pharmacology Antibodies Flow cytometry Mice 03 medical and health sciences 0302 clinical medicine Western blot Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans MTT assay Mice Inbred BALB C Chemotherapy medicine.diagnostic_test Chemistry General Medicine HCT116 Cells 021001 nanoscience & nanotechnology medicine.disease Xenograft Model Antitumor Assays In vitro Oxaliplatin Receptors TNF-Related Apoptosis-Inducing Ligand 030220 oncology & carcinogenesis MCF-7 Cells Gold 0210 nano-technology medicine.drug
Zdroj:	Drug Delivery. 23:3505-3519
ISSN:	1521-0464 1071-7544
DOI:	10.1080/10717544.2016.1199606
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a3a5d1cc693b4bb72c279d98a8996615 https://doi.org/10.1080/10717544.2016.1199606 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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