title: The potential use of H102 peptide-loaded dual-functional nanoparticles in the treatment of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a complex neurodegenerative disease with few effective treatments. The non-targeted distribution of drugs decreases drug efficiency and cause side effects. The cascade targeting strategy has been suggested for precise drug delivery. We developed a dual-functional nanoparticle drug delivery system loaded with β-sheet breaker peptide H102 (TQNP/H102). Two targeting peptides, TGN and QSH, were conjugated to the surface of the nanoparticles for blood-brain barrier transport and Aβ42 targeting, respectively. The prepared nanoparticles were spherical and uniform. The brain distribution study of H102 was conducted with the HPLC-mass spectrometry method to evaluate whether this nano-carrier could achieve increased AD-lesion delivery. The highest uptake of H102 was observed in the hippocampi of the TQNP/H102 group mice 1h after administration, which was 2.62 and 1.86 times the level of non-modified nanoparticles (NP/H102) and TGN modified nanoparticles (TNP/H102), respectively. The neuroprotective effects of H102 preparations were evaluated using Morris water maze experiment, biochemical indexes assay and tissue histology. The spatial learning and memory of the AD model mice in the TQNP/H102 group were significantly improved compared with the AD control group, and were also better than other preparations at the same dosage, even the TNP/H102 group. These results were consistent with the values of biochemical indexes in mouse hippocampi as well as the histological observations. The results demonstrate that TQNP is a promising carrier for peptide or protein drugs, such as H102, for entry into the central nervous system (CNS) and subsequent location of brain AD lesions, thus offering a highly-specific method for AD therapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China; Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, 201203, PR China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China; Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, 201203, PR China.
authors.forename: Xiaoyao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China; Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, 201203, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China; Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, 201203, PR China.
authors.forename: Xiayan
authors.initials: X
authors.lastname: Shao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China; Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, 201203, PR China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China; Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, 201203, PR China.
authors.forename: Zheming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China; Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, 201203, PR China. Electronic address: qzzhang@fudan.edu.cn.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D016503:Drug Delivery Systems; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism
chemical_list: D010455:Peptides; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols
keywords: Alzheimer's disease (AD); Aβ42; Dual-functional nanoparticles; H102 peptides