title: Delivery of Flightless I Neutralizing Antibody from Porous Silicon Nanoparticles Improves Wound Healing in Diabetic Mice.
abstract: Flightless I (Flii) is elevated in human chronic wounds and is a negative regulator of wound repair. Decreasing its activity improves healing responses. Flii neutralizing antibodies (FnAbs) decrease Flii activity in vivo and hold significant promise as healing agents. However, to avoid the need for repeated application in a clinical setting and to protect the therapeutic antibody from the hostile environment of the wound, suitable delivery vehicles are required. In this study, the use of porous silicon nanoparticles (pSi NPs) is demonstrated for the controlled release of FnAb to diabetic wounds. We achieve FnAb loading regimens exceeding 250 µg antibody per mg of vehicle. FnAb-loaded pSi NPs increase keratinocyte proliferation and enhance migration in scratch wound assays. Release studies confirm the functionality of the FnAb in terms of Flii binding. Using a streptozotocin-induced model of diabetic wound healing, a significant improvement in healing is observed for mice treated with FnAb-loaded pSi NPs compared to controls, including FnAb alone. FnAb-loaded pSi NPs treated with proteases show intact and functional antibody for up to 7 d post-treatment, suggesting protection of the antibodies from proteolytic degradation in wound fluid. pSi NPs may therefore enable new therapeutic approaches for the treatment of diabetic ulcers.
authors.affiliation: Wound Management Innovation Cooperative Research Centre, Future Industries Institute, University of South Australia, Adelaide, South Australia, 5001, Australia.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Turner
authors.affiliation: Wound Management Innovation Cooperative Research Centre, Future Industries Institute, University of South Australia, Adelaide, South Australia, 5001, Australia.
authors.forename: Steven J P
authors.initials: SJ
authors.lastname: McInnes
authors.affiliation: Wound Management Innovation Cooperative Research Centre, Future Industries Institute, University of South Australia, Adelaide, South Australia, 5001, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Melville
authors.affiliation: Wound Management Innovation Cooperative Research Centre, Future Industries Institute, University of South Australia, Adelaide, South Australia, 5001, Australia.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Cowin
authors.affiliation: Wound Management Innovation Cooperative Research Centre, Future Industries Institute, University of South Australia, Adelaide, South Australia, 5001, Australia.
authors.forename: Nicolas H
authors.initials: NH
authors.lastname: Voelcker
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D048909:Diabetes Complications / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D006801:Humans; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins; D053758:Nanoparticles; D012825:Silicon; D015534:Trans-Activators; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D057134:Antibodies, Neutralizing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D003692:Delayed-Action Preparations; C000609263:FlII protein, mouse; D008840:Microfilament Proteins; D015534:Trans-Activators; D012825:Silicon
keywords: chronic wounds; diabetes; flightless neutralizing antibodies; improved wound healing; porous silicon; protein therapeutics