title: Grapefruit-Derived Nanovectors Use an Activated Leukocyte Trafficking Pathway to Deliver Therapeutic Agents to Inflammatory Tumor Sites.
abstract: Inflammation is a hallmark of cancer. Activated immune cells are intrinsically capable of homing to inflammatory sites. Using three inflammatory-driven disease mouse models, we show that grapefruit-derived nanovectors (GNV) coated with inflammatory-related receptor enriched membranes of activated leukocytes (IGNVs) are enhanced for homing to inflammatory tumor tissues. Blocking LFA-1 or CXCR1 and CXCR2 on the IGNVs significantly inhibits IGNV homing to the inflammatory tissue. The therapeutic potential of IGNVs was further demonstrated by enhancing the chemotherapeutic effect as shown by inhibition of tumor growth in two tumor models and inhibiting the inflammatory effects of dextran sulfate sodium-induced mouse colitis. The fact that IGNVs are capable of homing to inflammatory tissue and that chemokines are overexpressed in diseased human tissue provides the rationale for using IGNVs to more directly deliver therapeutic agents to inflammatory tumor sites and the rationale for the use of IGNVs as treatment for certain cancers in personalized medicine.
authors.affiliation: Louisville Veterans Administration Medical Center, Louisville, Kentucky. James Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: James Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.affiliation: James Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky.
authors.forename: Nejat K
authors.initials: NK
authors.lastname: Egilmez
authors.affiliation: James Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: James Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: James Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: James Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: James Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky.
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.affiliation: Louisville Veterans Administration Medical Center, Louisville, Kentucky. James Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky. H0Zhan17@louisville.edu.
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D032083:Citrus paradisi; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000628:therapy; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology