The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application
Abstract
:1. Introduction
2. Results
2.1. Synthesis of bCDsuMema Conjugates
2.2. Fabrication and Characterization of Nanoparticles
2.3. In Vivo Biodistribution of Nanoparticles
2.4. The Effect of Oxidative Stress on the NMDAR1 Expression in SH-SY5Y Neuroblastoma Cells and U87MG Cells
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Synthesis of bCDsu-Thioketal-Memantine Conjugates
4.3. H Nuclear Magnetic Resonance (NMR) Spectra Measurement
4.4. Fabrication of bCDsuMema Nanoparticles
4.5. Characterization of Nanoparticles
4.6. Drug Release Study
4.7. Cell Culture
4.8. MTT Assay
4.9. Antibodies
4.10. Western Blot Assay
4.11. Fluorescence Microscopy
4.12. In Vivo Fluorescence Imaging
4.13. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Lugrin, J.; Rosenblatt-Velin, N.; Parapanov, R.; Liaudet, L. The role of oxidative stress during inflammatory processes. Biol. Chem. 2014, 395, 203–230. [Google Scholar] [CrossRef] [Green Version]
- Li, D.; Yang, Y.; Wang, S.; He, X.; Liu, M.; Bai, B.; Tian, C.; Sun, R.; Yu, T.; Chu, X. Role of acetylation in doxorubicin-induced cardiotoxicity. Redox Biol. 2021, 46, 102089. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.-W.; Dai, C.-M.; Chen, X.-H.; Feng, J.-F. The Relationship between Serum Trace Elements and Oxidative Stress of Patients with Different Types of Cancer. Oxidative Med. Cell. Longev. 2021, 2021, 1–13. [Google Scholar] [CrossRef]
- Uttara, B.; Singh, A.V.; Zamboni, P.; Mahajan, R.T. Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options. Curr. Neuropharmacol. 2009, 7, 65–74. [Google Scholar] [CrossRef] [Green Version]
- Yaribeygi, H.; Sathyapalan, T.; Atkin, S.L.; Sahebkar, A. Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus. Oxidative Med. Cell. Longev. 2020, 2020, 1–13. [Google Scholar] [CrossRef] [Green Version]
- Sun, Y.; Rawish, E.; Nording, H.; Langer, H. Inflammation in Metabolic and Cardiovascular Disorders—Role of Oxidative Stress. Life 2021, 11, 672. [Google Scholar] [CrossRef]
- Jimenez-Moreno, N.; Lane, J.D. Autophagy and Redox Homeostasis in Parkinson’s: A Crucial Balancing Act. Oxidative Med. Cell. Longev. 2020, 2020, 1–38. [Google Scholar] [CrossRef]
- Luca, M.; Luca, A.; Calandra, C. The Role of Oxidative Damage in the Pathogenesis and Progression of Alzheimer’s Disease and Vascular Dementia. Oxidative Med. Cell. Longev. 2015, 2015, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Chen, X.; Guo, C.; Kong, J. Oxidative stress in neurodegenerative diseases. Neural Regen. Res. 2012, 7, 376–385. [Google Scholar]
- Singh, A.; Kukreti, R.; Saso, L.; Kukreti, S. Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules 2019, 24, 1583. [Google Scholar] [CrossRef] [Green Version]
- Klein, J.A.; Ackerman, S.L. Oxidative stress, cell cycle, and neurodegeneration. J. Clin. Investig. 2003, 111, 785–793. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tejchman, K.; Kotfis, K.; Sieńko, J. Biomarkers and Mechanisms of Oxidative Stress—Last 20 Years of Research with an Emphasis on Kidney Damage and Renal Transplantation. Int. J. Mol. Sci. 2021, 22, 8010. [Google Scholar] [CrossRef] [PubMed]
- Betzen, C.; White, R.; Zehendner, C.M.; Pietrowski, E.; Bender, B.; Luhmann, H.J.; Kuhlmann, C.R. Oxidative stress upregulates the NMDA receptor on cerebrovascular endothelium. Free Radic. Biol. Med. 2009, 47, 1212–1220. [Google Scholar] [CrossRef]
- Cenini, G.; Lloret, A.; Cascella, R. Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View. Oxidative Med. Cell. Longev. 2019, 2019, 1–18. [Google Scholar] [CrossRef] [Green Version]
- Chiang, T.I.; Yu, Y.H.; Lin, C.H.; Lane, H.Y. Novel biomarkers of Alzheimer’s disease: Based upon N-methyl-d-aspartate receptor hypoactivation and oxidative stress. Clin. Psychopharmacol. Neurosci. 2021, 19, 423–433. [Google Scholar] [CrossRef]
- Umeno, A.; Biju, V.; Yoshida, Y. In vivo ROS production and use of oxidative stress-derived biomarkers to detect the onset of diseases such as Alzheimer’s disease, Parkinson’s disease, and diabetes. Free Radic. Res. 2017, 51, 413–427. [Google Scholar] [CrossRef] [PubMed]
- Persson, T.; Popescu, B.O.; Cedazo-Minguez, A. Oxidative Stress in Alzheimer’s Disease: Why Did Antioxidant Therapy Fail? Oxidative Med. Cell. Longev. 2014, 2014, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Simunkova, M.; Alwasel, S.H.; Alhazza, I.M.; Jomova, K.; Kollar, V.; Rusko, M.; Valko, M. Management of oxidative stress and other pathologies in Alzheimer’s disease. Arch. Toxicol. 2019, 93, 2491–2513. [Google Scholar] [CrossRef] [Green Version]
- Suh, W.H.; Suslick, K.S.; Suh, Y.H. Therapeutic agents for Alzheimer’s disease. Curr. Med. Chem. 2005, 5, 259–269. [Google Scholar]
- Yu, T.-W.; Lane, H.-Y.; Lin, C.-H. Novel Therapeutic Approaches for Alzheimer’s Disease: An Updated Review. Int. J. Mol. Sci. 2021, 22, 8208. [Google Scholar] [CrossRef]
- Cruz-Vicente, P.; Passarinha, L.; Silvestre, S.; Gallardo, E. Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches. Molecules 2021, 26, 2193. [Google Scholar] [CrossRef]
- Kamat, P.K.; Kalani, A.; Rai, S.; Swarnkar, S.; Tota, S.; Nath, C.; Tyagi, N. Mechanism of oxidative stress and synapse dys-function in the pathogenesis of Alzheimer’s disease: Understanding the therapeutics strategies. Mol. Neurobiol. 2016, 53, 648–661. [Google Scholar] [CrossRef] [Green Version]
- Ferreira, T.R.; Lopes, L.C.; Bergamaschi, C.d.C. Frequency and Severity of Adverse Drug Reactions to Medications Prescribed for Alzheimer’s Disease in a Brazilian City: Cross-Sectional Study. Front. Pharmacol. 2020, 11, 1966. [Google Scholar] [CrossRef] [PubMed]
- Mistry, V.M.; Morizio, P.L.; Pepin, M.J.; Bryan, W.E.; Brown, J.N. Role of memantine in the prophylactic treatment of episodic migraine: A systematic review. Headache J. Head Face Pain 2021, 61, 1207–1213. [Google Scholar] [CrossRef]
- Banks, W.A. Drug delivery to the brain in Alzheimer’s disease: Consideration of the blood-brain barrier. Adv. Drug Deliv. Rev. 2012, 64, 629–639. [Google Scholar] [CrossRef] [Green Version]
- Cheng, Z.; Zhang, J.; Liu, H.; Li, Y.; Zhao, Y.; Yang, E. Central nervous system penetration for small molecule therapeutic agents does not increase in multiple sclerosis- and Alzheimer’s disease-related animal models despite reported blood-brain barrier disruption. Drug Metab. Dispos. 2010, 38, 1355–1361. [Google Scholar] [CrossRef] [Green Version]
- Zhu, F.-D.; Hu, Y.-J.; Yu, L.; Zhou, X.-G.; Wu, J.-M.; Tang, Y.; Qin, D.-L.; Fan, Q.-Z.; Wu, A.-G. Nanoparticles: A Hope for the Treatment of Inflammation in CNS. Front. Pharmacol. 2021, 12, 1114. [Google Scholar] [CrossRef] [PubMed]
- Seo, M.-W.; Park, T.-E. Recent advances with liposomes as drug carriers for treatment of neurodegenerative diseases. Biomed. Eng. Lett. 2021, 11, 211–216. [Google Scholar] [CrossRef]
- Agrawal, M.; Prathyusha, E.; Ahmed, H.; Dubey, S.K.; Kesharwani, P.; Singhvi, G.; Naidu, V.G.M.; Alexander, A. Biomaterials in treatment of Alzheimer’s disease. Neurochem. Int. 2021, 145, 105008. [Google Scholar] [CrossRef] [PubMed]
- Fu, C.; Xiang, Y.; Li, X.; Fu, A. Targeted transport of nanocarriers into brain for theranosis with rabies virus glycoprotein-derived peptide. Mater. Sci. Eng. C Mater. Biol. Appl. 2018, 87, 155–166. [Google Scholar] [CrossRef]
- Mudshinge, S.R.; Deore, A.B.; Patil, S.; Bhalgat, C.M. Nanoparticles: Emerging carriers for drug delivery. Saudi Pharm. J. 2011, 19, 129–141. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vinod, C.; Jena, S. Nano-Neurotheranostics: Impact of Nanoparticles on Neural Dysfunctions and Strategies to Reduce Toxicity for Improved Efficacy. Front. Pharmacol. 2021, 12, 612692. [Google Scholar] [CrossRef]
- Li, X.; Tsibouklis, J.; Weng, T.; Zhang, B.; Yin, G.; Feng, G.; Cui, Y.; Savina, I.N.; Mikhalovska, L.I.; Sandeman, S.R.; et al. Nano carriers for drug transport across the blood–brain barrier. J. Drug Target. 2016, 25, 17–28. [Google Scholar] [CrossRef] [Green Version]
- Liu, Y.; Hong, H.; Xue, J.; Luo, J.; Liu, Q.; Chen, X.; Pan, Y.; Zhou, J.; Liu, Z.; Chen, T. Near-Infrared Radiation-Assisted Drug Delivery Nanoplatform to Realize Blood–Brain Barrier Crossing and Protection for Parkinsonian Therapy. ACS Appl. Mater. Interfaces 2021, 13, 37746–37760. [Google Scholar] [CrossRef] [PubMed]
- Cunha, A.; Gaubert, A.; Latxague, L.; Dehay, B. PLGA-Based nanoparticles for neuroprotective drug delivery in neuro-degenerative diseases. Pharmaceutics 2021, 13, 1042. [Google Scholar] [CrossRef] [PubMed]
- Singh, A.K.; Singh, S.S.; Rathore, A.S.; Singh, S.P.; Mishra, G.; Awasthi, R.; Mishra, S.K.; Gautam, V.; Singh, S.K. Lipid-coated MCM-41 mMesoporous silica nanoparticles loaded with berberine improved inhibition of acetylcholine esterase and amyloid formation. ACS Biomater. Sci. Eng. 2021, 7, 3737–3753. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.L.; Hwang, S.C.; Nah, J.W.; Kim, J.; Cha, B.; Kang, D.H.; Jeong, Y.I. Redox- and pH-responsive nanoparticles release piperlongumine in a stimuli-sensitive manner to inhibit pulmonary metastasis of colorectal carcinoma cells. J. Pharm. Sci. 2018, 107, 2702–2712. [Google Scholar] [CrossRef]
- Song, J.; Kook, M.-S.; Kim, B.-H.; Jeong, Y.-I.; Oh, K.-J. Ciprofloxacin-Releasing ROS-Sensitive Nanoparticles Composed of Poly(Ethylene Glycol)/Poly(D,L-lactide-co-glycolide) for Antibacterial Treatment. Materials 2021, 14, 4125. [Google Scholar] [CrossRef]
- Shen, Y.; Cao, B.; Snyder, N.R.; Woeppel, K.M.; Eles, J.R.; Cui, X.T. ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier. J. Nanobiotechnol. 2018, 16, 1–17. [Google Scholar] [CrossRef] [Green Version]
- Ballance, W.C.; Qin, E.C.; Chung, H.J.; Gillette, M.U.; Kong, H. Reactive oxygen species-responsive drug delivery systems for the treatment of neurodegenerative diseases. Biomaterials 2019, 217, 119292. [Google Scholar] [CrossRef]
- Alyaudtin, R.N.; Reichel, A.; Löbenberg, R.; Ramge, P.; Kreuter, J.; Begley, D.J. Interaction of poly(butylcyanoacrylate) nano-particles with the blood-brain barrier in vivo and in vitro. J. Drug Target. 2001, 9, 209–221. [Google Scholar] [CrossRef] [PubMed]
- Sun, D.; Xue, A.; Zhang, B.; Lou, H.; Shi, H.; Zhang, X. Polysorbate 80-coated PLGA nanoparticles improve the permeability of acetylpuerarin and enhance its brain-protective effects in rats. J. Pharm. Pharmacol. 2015, 67, 1650–1662. [Google Scholar] [CrossRef] [PubMed]
- Koffie, R.M.; Farrar, C.; Saidi, L.-J.; William, C.; Hyman, B.T.; Spires-Jones, T.L. Nanoparticles enhance brain delivery of blood-brain barrier-impermeable probes for in vivo optical and magnetic resonance imaging. Proc. Natl. Acad. Sci. USA 2011, 108, 18837–18842. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pang, Z.; Lu, W.; Gao, H.; Hu, K.; Chen, J.; Zhang, C.; Gao, X.; Jiang, X.; Zhu, C. Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26. J. Control. Release 2008, 128, 120–127. [Google Scholar] [CrossRef]
- Killian, D.M.; Gharat, L.; Chikhale, P.J.; Killian, L.G.D.M. Modulating Blood-Brain Barrier Interactions of Amino Acid-Based Anticancer Agents. Drug Deliv. 2000, 7, 21–25. [Google Scholar] [CrossRef]
- Killian, D.M.; Chikhale, P.J. A bioreversible prodrug approach designed to shift mechanism of brain uptake for amino-acid-containing anticancer agents. J. Neurochem. 2001, 76, 966–974. [Google Scholar] [CrossRef] [Green Version]
- Florendo, M.; Figacz, A.; Srinageshwar, B.; Sharma, A.; Swanson, D.; Dunbar, G.L.; Rossignol, J. Use of Polyamidoamine Dendrimers in Brain Diseases. Molecules 2018, 23, 2238. [Google Scholar] [CrossRef] [Green Version]
- Fana, M.; Gallien, J.; Srinageshwar, B.; Dunbar, G.L.; Rossignol, J. PAMAM Dendrimer Nanomolecules Utilized as Drug Delivery Systems for Potential Treatment of Glioblastoma: A Systematic Review. Int. J. Nanomed. 2020, 15, 2789–2808. [Google Scholar] [CrossRef] [Green Version]
- Pereira, P.; Barreira, M.; Cruz, C.; Tomás, J.; Luís, Â.; Pedro, A.Q.; Queiroz, J.A.; Sousa, F. Brain-targeted delivery of pre-miR-29b using lactoferrin-stearic acid-modified-chitosan/polyethyleneimine polyplexes. Pharmaceuticals 2020, 13, 314. [Google Scholar] [CrossRef]
- Sánchez-López, E.; Ettcheto, M.; Egea, M.A.; Espina, M.; Cano, A.; Calpena, A.C.; Camins, A.; Carmona, N.; Silva, A.M.; Souto, E.B.; et al. Memantine loaded PLGA PEGylated nanoparticles for Alzheimer’s disease: In vitro and in vivo characterization. J. Nanobiotechnol. 2018, 16, 32. [Google Scholar] [CrossRef]
- Hu, X.-L.; Gao, L.-Y.; Niu, Y.-X.; Tian, X.; Wang, J.; Meng, W.-H.; Zhang, Q.; Cui, C.; Han, L.; Zhao, Q.-C. Neuroprotection by Kukoamine A against oxidative stress may involve N-methyl-d-aspartate receptors. Biochim. Biophys. Acta (BBA)-Gen. Subj. 2015, 1850, 287–298. [Google Scholar] [CrossRef] [PubMed]
- Tian, X.; Gao, L.; An, L.; Jiang, X.; Bai, J.; Huang, J.; Meng, W.; Zhao, Q. Pretreatment of MQA, a caffeoylquinic acid derivative compound, protects against H2O2-induced oxidative stress in SH-SY5Y cells. Neurol. Res. 2016, 38, 1079–1087. [Google Scholar] [CrossRef] [PubMed]
- Rosini, M.; Simoni, E.; Caporaso, R.; Basagni, F.; Catanzaro, M.; Abu, I.F.; Fagiani, F.; Fusco, F.; Masuzzo, S.; Albani, D.; et al. Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer’s disease. Eur. J. Med. Chem. 2019, 180, 111–120. [Google Scholar] [CrossRef] [PubMed]
- Park, J.S.; Choi, H.-I.; Kim, D.-H.; Kim, C.S.; Bae, E.H.; Ma, S.K.; Kim, S.W. RON Receptor Tyrosine Kinase Regulates Epithelial Mesenchymal Transition and the Expression of Pro-Fibrotic Markers via Src/Smad Signaling in HK-2 and NRK49F Cells. Int. J. Mol. Sci. 2019, 20, 5489. [Google Scholar] [CrossRef] [Green Version]
Memantine Contents (%, w/w) | Particle Size (nm) | ||
---|---|---|---|
Theoretical * | Experimental | ||
bCDsuMema conjugates | 9.4 | 9.1 | 82.8 ± 12.3 |
H2O2 Contents (mM) | Particle Size Distribution | Polydispersity | |
---|---|---|---|
Diameter ± S.D. (nm) | % Intensity | ||
1 | 103.7 ± 35.68 | 93.1 | 0.271 |
4603 ± 826.2 | 6.9 | ||
5 | 31.32 ± 7.833 | 9.7 | 0.283 |
155.3 ± 74.28 | 90.3 | ||
10 | 137.5 ± 80.97 | 96.9 | 0.268 |
4599 ± 828.3 | 3.1 |
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Park, J.S.; Kim, T.; Kim, D.; Jeong, Y.-I. The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application. Int. J. Mol. Sci. 2021, 22, 12309. https://doi.org/10.3390/ijms222212309
Park JS, Kim T, Kim D, Jeong Y-I. The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application. International Journal of Molecular Sciences. 2021; 22(22):12309. https://doi.org/10.3390/ijms222212309
Chicago/Turabian StylePark, Jung Sun, Taeyeon Kim, Dohoon Kim, and Young-IL Jeong. 2021. "The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application" International Journal of Molecular Sciences 22, no. 22: 12309. https://doi.org/10.3390/ijms222212309