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Synergistic effects of IL-3 release and Mn2+-doped Prussian blue nanoparticles camouflaged with MES23.5 cell membranes on Alzheimer’s disease therapy
Nano Research 2025, 18(2): 94907175
Published: 06 January 2025
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder with prolonged latency during the prodromal stage. However, current clinical approaches to pharmacological interventions for AD remain challenge. An effective treatment strategy is to eliminate protein aggregates and prevent their regeneration. In this study, interleukin (IL)-3-loaded porous manganese (Mn2+)-doped Prussian blue (PB) nanoparticles (NPs) were coated with dopaminergic MES23.5 neuronal cell membranes (PBMn-IL3@CM) and then used to combat AD progression. The PBMn-IL3@CM NPs possessed a high targeting efficiency, being able to traverse the blood-brain barrier and specifically affect the brain to reduce oxidative stress. The Mn2+-doped PB NPs effectively scavenged reactive oxygen radicals produced by microglia, inducing the pro-inflammatory M1 microglia. In addition, the released IL-3 activated microglia, causing the polarization of the M1 phenotype to the anti-inflammatory M2 phenotype in vitro and in vivo. The transition reduced phosphorylated tau accumulation, mediated neurotoxicity, and eliminated tau aggregates, which reversed cognitive impairment in AD mice. The PBMn-IL3@CM NPs showed excellent biocompatibility without significant adverse effects; consequently, they represent a promising AD treatment.

Research Article Issue
Hyaluronic acid-based dual-responsive nanomicelles mediated mutually synergistic photothermal and molecular targeting therapies
Nano Research 2022, 15(7): 6361-6371
Published: 07 May 2022
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Precise clinical treatment of triple-negative breast cancer (TNBC) is an obstacle in clinic. Nanotechnology-assisted photothermal therapy (PTT) is a superior treatment modality for TNBC in terms of precision. However, thermoresistance arising from PTT and insufficient drug release from nanocarriers decrease the efficacy of PTT. AT13387 is a novel HSP90 inhibitor that can weaken thermoresistance and undergoing clinic II phase study, showing satisfactory antitumour activity through molecularly targeted therapy (MTT). Whereas, it has poor solubility. Hence hyaluronic acid and stearic acid were connected by hydrazone bonds and disulfide bonds, forming an amphipathic copolymer that could self-assembled into nanomicelles, followed by encapsulating Cypate and AT13387. These nanomicelles exhibited great features, including achieving mutually synergistic PTT/MTT for overcoming thermoresistance and promoting translocation of drugs, increasing the solubility of Cypate and AT13387, showing a pH/redox dual response that contributes to drug release, and having the ability of active targeting. Thus, the nanomicelles developed in this study may be a promising strategy for the precise treatment of TNBC.

Research Article Issue
Polydopamine functionalized mesoporous silica as ROS-sensitive drug delivery vehicles for periodontitis treatment by modulating macrophage polarization
Nano Research 2021, 14(12): 4577-4583
Published: 09 March 2021
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Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culminates in periodontal destruction. In this study, a novel ROS-responsive drug delivery system based on polydopamine (PDA) functionalized mesoporous silica nanoparticles was developed for delivering minocycline hydrochloride (MH) to treat periodontitis. The outer PDA layer and the inner MH of the nanoparticles acted as ROS scavengers and anti-inflammatory agents, respectively. Under the synergistic action of PDA and MH, macrophages were polarized from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. The in vitro experiments provided convincing evidence that PDA could scavenge ROS effectively, and the expression of pro-inflammatory cytokines was attenuated and the secretion of anti-inflammatory cytokines was enhanced through M1 to M2 polarization of macrophages with the cooperation of MH. In addition, the results obtained from the periodontitis rat models demonstrated that the synergetic effect of PDA and MH prevented alveolar bone loss without causing any adverse effect. Taken together, the results from the present investigation provide a new strategy to remodel the inflammatory microenvironment by inducing the polarization of macrophages from M1 toward M2 state for the treatment of periodontitis.

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