Ultrasmall Coordination Polymers for Alleviating ROS-Mediated Inflammatory and Realizing Neuroprotection against Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease globally, and there is currently no effective treatment for this condition. Excessive accumulation of reactive oxygen species (ROS) and neuroinflammation are major contributors to PD pathogenesis. Herein, ultrasmall nanoscale coordination polymers (NCPs) coordinated by ferric ions and natural product curcumin (Cur) were exploited, showing efficient neuroprotection by scavenging excessive radicals and suppressing neuroinflammation. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse PD model, such ultrasmall Fe-Cur NCPs with prolonged blood circulation and BBB traversing capability could effectively alleviate oxidative stress, mitochondrial dysfunction, and inflammatory condition in the midbrain and striatum to reduce PD symptoms. Thus, this study puts forth a unique type of therapeutics-based NCPs that could be used for safe and efficient treatment of PD with potential in clinical translation.

Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

“…Triple-targeting micelle SHR [ 280] SS31 SS31 RVG29;neutrophil-like (HL-60) cell membranes -6-10 11.99 ± 1.23 -Neuronal damage MSC-EVs [ 203] --124.3 -miRNAs PD MSCEXO/PMA [ 259] MSCEO High ROS 143 ≈-25 NO PD PBzyme [ 260] Intra-cerebroventricular injection -≈106 -17 PBzyme PD Lf-Au-Bi 2 Se 3 NDs [ 261] Lactoferrin -6-9 ≈-25 -PD TFNAs [ 282] --≈15 -ssDNA PD RVG29-RBCm/Cur-NCs [278] RVG29 -84.3 -20.94 Curcumin PD Fe-Cur NCPs [ 283] Ultra-small size; amphipathy -≈10 ≈-15 Iron-based enzyme; Curcumin PD CSCCT NPs [ 201] -TPP 47.6 ± 7.5 -23 (CSP-Cur) Curcumin PD GER-UDCA-SLNs [284] SLNs -121 ± 8.4 -22.5 ± 7.7 Geraniol; Ursodeoxycholic acid TBI C3/SS31-RBCNLCs-Ola [107] C3 Peptide SS31 126.23 ± 0.94 -9.66 ± 0.43 Olapani TBI TPP-D-NAC [255] PAMAM TPP 7.5 ± 0.2 16.9 ± 0.4 NAC SCI nano-SOD/CAT [285] SCI -293 ± 6.4 -17.1 ± 1.5 SOD; CAT mitophagy to effectively counteract AKI. [207] Adropin (Ad)-loaded nanocapsules (Ad@Gel, Figure 17B) regulated glucose and fatty acid metabolism in renal, and improved mitochondrial functions by up-regulating neuronatin (Nnat) expression and down-regulating translocator protein (TSPO) expression of di-abetic mice (Figure 17C-F).…”

Parkinson's Disease: Current Status, Diagnosis, and Treatment Using Nanomedicines

“…This antioxidant therapy holds promise for clinical translation and application in the safe and effective treatment of PD ( Figure ). [ 110 ] The design and development of nanomedicines, such as nanoparticles conjugated with antioxidative drugs, will demonstrate effective treatment of PD and reduction of α‐synuclein levels shortly.…”

“…(K) Anti-Parkinsonism mechanism. Reproduced under the terms of the Creative Commons Attribution License (CC BY) [110]. Copyright 2022, The Authors, published by AAAS.…”

Enzyme Core Spherical Nucleic Acid That Enables Enhanced Cuproptosis and Antitumor Immune Response through Alleviating Tumor Hypoxia

“…First, inducing disruption of copper homeostasis is challenging due to the low intracellular “copper source”. To overcome this, a promising approach is the selective delivery of exogenous copper to mitochondria using copper ion carriers. − Furthermore, cuproptosis primarily affects the TCA cycle, whereas tumor cells often rely heavily on glycolysis for energy production, especially under hypoxic conditions, which results in obvious inhibition of cuproptosis. − To the best of our knowledge, there have been no reports of enhancing mitochondrial respiration by increasing intracellular oxygen levels as an effective strategy to promote cuproptosis.…”