title: Pro-apoptotic activity of nano-escheriosome based oleic acid conjugate against 7,12-dimethylbenz(a)anthracene (DMBA) induced cutaneous carcinogenesis.
abstract: OBJECTIVE
  2,6-Diisopropylphenol-oleic acid (2,6P-OLA) is an ester conjugate of oleic acid that has displayed a strong anticancer activity on different types of cancer cell lines (Khan et al., 2012). The present study is focused on the development of a nano-liposome-based approach for the delivery of 2,6P-OLA on 7,12-dimethylbenz(a)anthracene (DMBA) induced cutaneous papilloma in experimental mice. For effective and specific delivery of the conjugate to the tumor site, it was incorporated into escheriosome (EC); an Escherichia coli lipid nanoparticle.
  
  
  METHODS
  I determined the size, zeta-potential, entrapment and release efficacy of 2,6P-OLA-EC nano-formulation. The consequence of 2,6P-OLA-EC treatment was initially analyzed by regression in tumor volume, inhibition of cutaneous papilloma and survival of treated mice. Its anticancer activity was further examined by histopathology, fluorescence microscopy, flow cytometry and electroblot-immuno assay of apoptotic factors.
  
  
  RESULTS
  Distinct disperse circular shaped EC nanoparticles showed slow and sustained release of therapeutic concentration of 2,6P-OLA in the surrounding milieu. 2,6P-OLA-EC significantly reduced tumor volume and inhibited onset of new papilloma. Treatment with nano-formulation revealed induced caspase-9 activity and noteworthy apoptotic response as visualized by fluorescence microscopy and TUNEL assay. Electroblot-immuno analysis revealed significant modulation of p53wt and p53mut expression levels.
  
  
  CONCLUSIONS
  The results suggest the therapeutic potential of 2,6P-OLA entrapped in nano-escheriosomes against cutaneous papilloma and can become a promising system against various forms of cancer as well.
authors.affiliation: Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: azmatbiotech@gmail.com.
authors.forename: Azmat Ali
authors.initials: AA
authors.lastname: Khan
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D063646:Carcinogenesis / Q000139:chemically induced* / Q000187:drug effects*; D008081:Liposomes / Q000494:pharmacology; D008297:Male; D051379:Mice; D023421:Models, Animal; D053758:Nanoparticles / Q000737:chemistry; D019301:Oleic Acid / Q000494:pharmacology*; D010212:Papilloma / Q000139:chemically induced / Q000188:drug therapy; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D019301:Oleic Acid; D015127:9,10-Dimethyl-1,2-benzanthracene
keywords: Anticancer agent; Escheriosome; Nano-formulation; Oleic acid conjugate; Skin papilloma; Topical application