title: Targeted tumor delivery and controlled release of neuronal drugs with ferritin nanoparticles to regulate pancreatic cancer progression.
abstract: Pancreatic cancer is a lethal malignancy whose progression is highly dependent on the nervous microenvironment. This study develops neural drug-loaded ferritin nanoparticles (Ft NPs) to regulate the nervous microenvironment, in order to control the pancreatic cancer progression. The drug-loaded Ft NPs can target pancreatic tumors via passive targeting of EPR effects of tumors and active targeting via transferrin receptor 1 (TfR1) binding on cancer cells, with a triggered drug release in acidic tumor environment. Two drugs, one activates neural activity (carbachol), the other impairs neural activity (atropine), are encapsulated into the Ft NPs to form two kinds of nano drugs, Nano-Cab NPs and Nano-Ato NPs, respectively. The activation of the nervous microenvironment by Nano-Cab NPs significantly promotes the pancreatic tumor progression, whereas the blockage of neural niche by Nano-Ato NPs remarkably impairs the neurogenesis in tumors and the progression of pancreatic cancer. The Ft-based nanoparticles thus comprise an effective and safe route of delivery of neural drugs for novel anti-cancer therapy.
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Liman
authors.initials: L
authors.lastname: Cong
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Nuoxin
authors.initials: N
authors.lastname: Wang
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing 100190, China. Electronic address: zhengwf@nanoctr.cn.
authors.forename: Wenfu
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing 100190, China. Electronic address: xingyujiang@nanoctr.cn.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001285:Atropine / Q000008:administration & dosage*; D002217:Carbachol / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005293:Ferritins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018721:Muscarinic Agonists / Q000008:administration & dosage*; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D053758:Nanoparticles / Q000008:administration & dosage*; D055495:Neurogenesis / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D001285:Atropine; D004317:Doxorubicin; D002217:Carbachol; D005293:Ferritins
keywords: Drug delivery; Ferritin nanoparticles; Nervous microenvironment; Pancreatic cancer