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Manganese Dioxide Nanoparticles Protect Cartilage From Inflammation-induced Oxidative Stress.
S. Kumar, Isaac M. Adjei, Shannon B. Brown, O. Liseth, B. Sharma
Published 2019 · Chemistry, Medicine
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Oxidative stress has been implicated in the pathogenesis of osteoarthritis and has become an important therapeutic target. Investigations of various antioxidant supplements, reactive oxidative species (ROS) pathway mediators, and free radical scavengers for treating osteoarthritis have demonstrated common disadvantages including poor bioavailability and stability, as well as rapid joint clearance or release profiles from delivery vehicles. Moreover, these therapies do not target cartilage, which irreversibly degenerates in the presence of oxidative stress. The goal of this study was to engineer a nanoparticle system capable of sustained retention in the joint space, localization to cartilage, and mitigation of oxidative stress. Towards this goal, ROS scavenging manganese dioxide nanoparticles with physicochemical properties (less than 20 nm and cationic) that facilitate their uptake into cartilage were developed and characterized. These particles penetrated through the depth of cartilage explants and were found both in the extracellular matrix as well as intracellularly within the resident chondrocytes. Furthermore, the particles demonstrated chondroprotection of cytokine-challenged cartilage explants by reducing the loss of glycosaminoglycans and release of nitric oxide. Quantitative PCR analysis revealed that the particles mitigated impacts of oxidative stress related genes in cytokine-challenged chondrocytes. When injected intra-articularly into rats, the particles persisted in the joint space over one week, with 75% of the initial signal remaining in the joint. Biodistribution and histological analysis revealed accumulation of particles at the chondral surfaces and colocalization of the particles with the lacunae of chondrocytes. The results suggest that the manganese dioxide nanoparticles could be a promising approach for the chondroprotection of osteoarthritic cartilage.
This paper references
Charge based intra-cartilage delivery of single dose dexamethasone using Avidin nano-carriers suppresses cytokine-induced catabolism long term.
A. Bajpayee (2016)
Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics
V. Natarajan (2015)
Deficiency of Nrf2 accelerates the effector phase of arthritis and aggravates joint disease.
N. Maicas (2011)
Rotenone prevents impact‐induced chondrocyte death
W. Goodwin (2010)
Effects of interleukin-1beta on chondroblast viability and extracellular matrix changes in bovine articular cartilage explants.
G. Stabellini (2003)
Mechanism of decomposition of hydrogen peroxide solutions with manganese dioxide.
D. Broughton (1947)
Cellular events leading to chondrocyte death after cartilage impact injury.
D. Green (2006)
Early and stable upregulation of collagen type II, collagen type I and YKL40 expression levels in cartilage during early experimental osteoarthritis occurs independent of joint location and histological grading
H. Lorenz (2005)
Cartilage-penetrating nanocarriers improve delivery and efficacy of growth factor treatment of osteoarthritis
Brett C Geiger (2018)
Cartilage-targeting drug delivery: can electrostatic interactions help?
A. Bajpayee (2017)
In vitro toxicity of nanoparticles in BRL 3A rat liver cells.
S. Hussain (2005)
Projections of US prevalence of arthritis and associated activity limitations.
J. Hootman (2006)
The complex pathology of osteoarthritis: even mitochondria are involved.
H. Roach (2008)
Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues.
Armin Vedadghavami (2018)
Effects of a Single Intra-Articular Injection of a Microsphere Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain
P. Conaghan (2018)
A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology
B. Rose (2016)
Detection of protein and mRNA of various components of the NADPH oxidase complex in an immortalized human chondrocyte line.
P. Moulton (1997)
MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx.
D. Candas (2014)
Osteoarthritis: an update with relevance for clinical practice
J. Bijlsma (2011)
Beneficial effects of cerium oxide nanoparticles in development of chondrocyte-seeded hydrogel constructs and cellular response to interleukin insults.
Detection of superoxide and NADPH oxidase in porcine articular chondrocytes.
T. Hiran (1997)
Oxygen and reactive oxygen species in cartilage degradation: friends or foes?
Y. Henrotin (2005)
Targeting oxidative stress to reduce osteoarthritis
B. Poulet (2016)
Synthesis and characterization of hyaluronic acid coated manganese dioxide microparticles that act as ROS scavengers.
J. Bizeau (2017)
Thioredoxin 1 is associated with the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes
T. Lu (2017)
Evaluation of Anti-Arthritic Property of Methotrexate Conjugated Gold Nanoparticle on Experimental Animal Models
A. Gomes (2013)
Toxicological Profile for Manganese
M. Williams (2012)
Double-knockout of ADAMTS-4 and ADAMTS-5 in mice results in physiologically normal animals and prevents the progression of osteoarthritis.
M. Majumdar (2007)
The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis
J. Buckwalter (2013)
Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses
Guangbao Yang (2017)
Particle-based technologies for osteoarthritis detection and therapy
Taylor E Kavanaugh (2015)
Manganese oxide particles as cytoprotective, oxygen generating agents.
Mohammad Hossein Tootoonchi (2017)
Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.
R. Lawrence (2008)
Intra-articular targeting of nanomaterials for the treatment of osteoarthritis.
Shannon Brown (2019)
Development of Optimized Copolymers and Delivery Formulations to Scavenge Reactive Oxygen Species and Prevent Joint Damage from Post-Traumatic Osteoarthritis
Taylor E Kavanaugh (2017)
Measurements of the Effective Diffusion Coefficient of Oxygen in Pancreatic Islets
E. Avgoustiniatos (2007)
Confocal imaging-guided laser ablation of basal cell carcinomas: an ex vivo study.
H. Sierra (2015)
Orthopaedic wear particle-induced bone loss and exogenous macrophage infiltration is mitigated by local infusion of NF-κB decoy oligodeoxynucleotide.
Tzuhua Lin (2017)
Preparation of MnO2 nanoparticles by directly mixing potassium permanganate and polyelectrolyte aqueous solutions
Yonglan Luo (2007)
Measurement of co‐localization of objects in dual‐colour confocal images
E. M. Manders (1993)
Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis.
A. Bajpayee (2014)
Poly(PS-b-DMA) micelles for reactive oxygen species triggered drug release.
M. Gupta (2012)
Intelligent Albumin-MnO2 Nanoparticles as pH-/H2 O2 -Responsive Dissociable Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy.
Q. Chen (2016)
In vitro eradication of citrullinated protein specific B-lymphocytes of rheumatoid arthritis patients by targeted bifunctional nanoparticles
Judit Pozsgay (2016)
A rabbit model demonstrates the influence of cartilage thickness on intra‐articular drug delivery and retention within cartilage
A. Bajpayee (2015)
Effect of resveratrol on cartilage protection and apoptosis inhibition in experimental osteoarthritis of rabbit
J. Wang (2010)
A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development
Y. Shi (2019)
Flow through interstitium and other fibrous matrices.
J. Levick (1987)
Cell protective, ABC triblock polymer-based thermoresponsive hydrogels with ROS-triggered degradation and drug release.
M. Gupta (2014)
Benefits of antioxidant supplements for knee osteoarthritis: rationale and reality
A. Grover (2015)
Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet
P. Bunney (2017)
Oxygen-generating Hybrid Polymeric Nanoparticles with Encapsulated Doxorubicin and Chlorin e6 for Trimodal Imaging-Guided Combined Chemo-Photodynamic Therapy
Danrong Hu (2018)
Multifunctional albumin-MnO₂ nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response.
P. Prasad (2014)
Intra-articular injection of an antioxidant formulation did not improve structural degeneration in a rat model of post-traumatic osteoarthritis
Yau-Chuk Cheuk (2017)
Nanoparticles with dual responses to oxidative stress and reduced ph for drug release and anti-inflammatory applications.
Hsiao-Lan Pu (2014)
Effect of gold nanoparticles in the treatment of established collagen arthritis in rats.
L. Leonavičienė (2012)
Electrostatic interactions enable rapid penetration, enhanced uptake and retention of intra‐articular injected avidin in rat knee joints
A. Bajpayee (2014)
Clinical comparison of orgotein and methylprednisolone acetate in the treatment of osteoarthrosis of the knee joint.
W. Gammer (1984)
Manganese-Induced Parkinsonism and Parkinson’s Disease: Shared and Distinguishable Features
Gunnar F. Kwakye (2015)
Development and In Vitro Evaluation of an Innovative “Dietary Flavonoid Supplement” on Osteoarthritis Process
M. R. Lauro (2017)
The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse.
S. Glasson (2010)
Ageing and the pathogenesis of osteoarthritis
R. Loeser (2016)
Extracellular superoxide dismutase and oxidant damage in osteoarthritis.
E. Regan (2005)
ROS-responsive microspheres for on demand antioxidant therapy in a model of diabetic peripheral arterial disease.
K. Poole (2015)
The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials.
P. Canter (2007)
MR tracking of transplanted cells with “positive contrast” using manganese oxide nanoparticles
A. A. Gilad (2008)
Progress in intra-articular therapy
C. H. Evans (2014)
Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis.
I. Mazzetti (2001)
Modulation of Hypoxia in Solid Tumor Microenvironment with MnO2 Nanoparticles to Enhance Photodynamic Therapy
W. Zhu (2016)
Oxygen radicals, inflammation, and arthritis: pathophysiological considerations and implications for treatment.
R. Greenwald (1991)
MnO2-Based Nanoplatform Serves as Drug Vehicle and MRI Contrast Agent for Cancer Theranostics.
Mei Zhang (2017)
Effect of resveratrol in experimental osteoarthritis in rabbits
N. Elmalı (2004)
N-acetylcysteine inhibits post-impact chondrocyte death in osteochondral explants.
J. Martin (2009)
Interleukin-1beta and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes: a possible explanation for oxidative stress generation.
M. Mathy-Hartert (2008)
A graphic user interface for the evaluation of knee osteoarthritis (GEKO): an open-source tool for histological grading.
H. E. Kloefkorn (2019)
Controlled Release of an Anti-inflammatory Drug Using an Ultrasensitive ROS-Responsive Gas-Generating Carrier for Localized Inflammation Inhibition.
Ming-Fan Chung (2015)
Therapeutic potential of curcumin in digestive diseases.
P. Dulbecco (2013)
The Interleukin 1β Pathway in the Pathogenesis of Osteoarthritis
Massoud Daheshia (2008)
The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer☆
E. Kansanen (2013)
Intra‐articular resveratrol injection prevents osteoarthritis progression in a mouse model by activating SIRT1 and thereby silencing HIF‐2α
W. Li (2015)
Aging processes and the development of osteoarthritis
R. Loeser (2013)
Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide.
R. Loeser (2006)
Osteoarthritis and nitric oxide.
S. Abramson (2008)
Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage.
Dominique A. Rothenfluh (2008)
Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with osteoarthritis.
C. Davies (2008)
ROS/oxidative stress signaling in osteoarthritis.
Panagiotis Lepetsos (2016)
Mechanisms of nanotoxicity: generation of reactive oxygen species.
P. Fu (2014)
Targeting aging for disease modification in osteoarthritis
J. A. Collins (2018)
ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro
H. Stanton (2005)
Effect of proteoglycan removal on solute mobility in articular cartilage.
P. Torzilli (1997)
Different cytotoxic and apoptotic responses of MCF-7 and HT1080 cells to MnO2 nanoparticles are based on similar mode of action.
Hisham A Alhadlaq (2019)
Bioconjugated Manganese Dioxide Nanoparticles Enhance Chemotherapy Response by Priming Tumor-Associated Macrophages toward M1-like Phenotype and Attenuating Tumor Hypoxia.
Manli Song (2016)
Therapeutic benefits of oxygen radical scavenger treatments remain unproven.
R. Greenwald (1985)
Nanoparticle Properties for Delivery to Cartilage: The Implications of Disease State, Synovial Fluid, and Off-Target Uptake.
Shannon Brown (2019)
The diagnosis of manganese-induced parkinsonism.
M. Cersosimo (2006)
This paper is referenced by
Keeping nanoparticles within the joint
A. Curtis (2019)
Physiological, transcriptomic, and metabolomic analyses reveal zinc oxide nanoparticles modulate plant growth in tomato
Liangliang Sun (2020)
Mn3O4 nanozymes boost endogenous antioxidant metabolites in cucumber (Cucumis sativus) plant and enhance resistance to salinity stress
L. Lu (2020)
Metal ion-responsive nanocarrier derived from phosphonated calixarenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage
M. Li (2020)
Injectable redox and light responsive MnO2 hybrid hydrogel for simultaneous melanoma therapy and multidrug-resistant bacteria-infected wound healing.
S. Wang (2020)
Nanostructured manganese dioxide for anticancer applications: preparation, diagnosis, and therapy.
Z. Zhang (2020)
Dual enzyme-like activities of transition metal-doped MnO2 nanocoatings and their dependence on the electronic band structure and ionic dissolution
Shiwei Liu (2020)