title: Blocking Interleukin-4 Receptor α Using Polyethylene Glycol Functionalized Superparamagnetic Iron Oxide Nanocarriers to Inhibit Breast Cancer Cell Proliferation.
abstract: OBJECTIVE
  The specific targeting of interleukin-4 receptor α (IL4Rα) receptor offers a promising therapeutic approach for inhibition of tumor cell progression in breast cancer patients. In the current study, thein vitroefficacy of superparamagnetic iron oxide nanoparticles conjugated with anti-IL4Rα blocking antibodies (SPION-IL4Rα) via polyethylene glycol polymers was evaluated in 4T1 breast cancer cells.
  
  
  METHODS
  Cell viability, reactive oxygen species generation, and apoptosis frequency were assessedin vitroin 4T1 cancer cell lines following exposure to SPION-IL4Rα alone or combined with doxorubicin. In addition, immunofluorescence assessments and fluorimetrywere performed to confirm the specific targeting and interaction of the developed nanocarriers with IL4Rα receptors in breast cancer cells.
  
  
  RESULTS
  Blocking of IL4Rα receptors caused a significant decrease in cell viability and induced apoptosis in 4T1 cells. In addition, combined treatment with SPION-IL4Rα+doxorubicin caused significant increases in cell death, apoptosis, and oxidative stress compared to either SPION-IL4Rα or doxorubicin alone, indicating the enhanced therapeutic efficacy of this combination. The decrease in fluorescence intensity upon immunofluorescence and fluorimetry assays combined with increased viability and decreased apoptosis following the blocking of IL4Rα receptors confirmed the successful binding of the synthesized nanocarriers to the target sites on murine 4T1 breast cancerous cells.
  
  
  CONCLUSIONS
  These results suggest that SPION-IL4Rα nanocarriers might be used for successfulreduction of tumor growth and inhibition of progression of metastasisin vivo.
authors.affiliation: Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abjal Pasha
authors.initials: AP
authors.lastname: Shaik
authors.affiliation: Prince Naif Health Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Asma Sultana
authors.initials: AS
authors.lastname: Shaik
authors.affiliation: Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ali Al
authors.initials: AA
authors.lastname: Majwal
authors.affiliation: Department of Radiological Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Achraf Al
authors.initials: AA
authors.lastname: Faraj
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D016503:Drug Delivery Systems; D015195:Drug Design; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D053662:Interleukin-4 Receptor alpha Subunit / Q000037:antagonists & inhibitors*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D018384:Oxidative Stress; D011092:Polyethylene Glycols / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D005290:Ferric Compounds; D053662:Interleukin-4 Receptor alpha Subunit; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C000499:ferric oxide; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Biomarkers; Breast neoplasms; Dextran coated superparamagnetic iron oxide; Drug delivery systems; Interleukin-4; Receptors; Tumor