title: Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody.
abstract: Despite recent advances in melanoma treatment through the use of anti-PD-1 (aPD1) immunotherapy, the efficacy of this method remains to be improved. Here we report an innovative self-degradable microneedle (MN) patch for the sustained delivery of aPD1 in a physiologically controllable manner. The microneedle is composed of biocompatible hyaluronic acid integrated with pH-sensitive dextran nanoparticles (NPs) that encapsulate aPD1 and glucose oxidase (GOx), which converts blood glucose to gluconic acid. The generation of acidic environment promotes the self-dissociation of NPs and subsequently results in the substantial release of aPD1. We find that a single administration of the MN patch induces robust immune responses in a B16F10 mouse melanoma model compared to MN without degradation trigger or intratumoral injection of free aPD1 with the same dose. Moreover, this administration strategy can integrate with other immunomodulators (such as anti-CTLA-4) to achieve combination therapy for enhancing antitumor efficacy.
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: Hochu
authors.affiliation: Department of Forest Biomaterials, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Hasan
authors.initials: H
authors.lastname: Sadeghifar
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.|Department of Medicine, University of North Carolina School of Medicine , Chapel Hill, North Carolina 27599, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D007167:Immunotherapy / Q000295:instrumentation / Q000379:methods; D051379:Mice; D009339:Needles; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D000912:Antibodies, Neoplasm; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor
keywords: Anti-PD-1; cancer immunotherapy; drug delivery; melanoma; microneedle patch