Platelet Membrane–Encapsulated MSNs Loaded with SS31 Peptide Alleviate Myocardial Ischemia-Reperfusion Injury
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
- MSN (purchased from Merck, Kenyos, NJ, USA)
- SS31 (purchased from Nanjing Jill Chemical Co., Ltd., Nanjing, China)
- DMEM medium (purchased from Hyclone, Utah Logan, UT, USA)
- Trypsin
- Super grade fetal bovine serum
- DMEM medium (purchased from GIBCO, Karlsbad, CA, USA)
- CCK8 enhanced reagent
- Reactive oxygen species detection kit
- Enhanced JC-1 detection kit
- Evans blue, 2, 3, 5-triphenyl tetrazole chloride (TTC)
- Recombinant anti-Bax antibody
- Recombinant anti–cytochrome-C antibody
- Recombinant anti–caspase-3 antibody, rabbit anti-mouse APAF antibody
- Rabbit anti-rat Bcl-2 antibody
- Rabbit anti-rat caspase-9 antibody
- Malondialdehyde kit
- Rat SOD ELISA kit
- Rat CK-MB ELISA kit
- Rat cTnT ELISA Kit (purchased from Beyotime Biotechnology, Shanghai, China)
- PGE1(purchased from Roche, Basel, Switzerland)
- Male Sprague-Dawley (SD) rats (purchased from Chengdu Dossy Experimental Animals Co., Ltd., Chengdu, China)
- Rat cardiomyoblast-derived cells (H9c2; purchased from Procell Life Science & Technology Co., Ltd., Wuhan, China))
2.2. Methods
2.2.1. PLTM Preparation
2.2.2. Synthesis of SS31/MSN@PLTM
2.2.3. SS31/MSN@PLTM Characterization
2.2.4. Cell Culture
2.2.5. Toxicity Studies on SS31/MSN@PLTM
2.2.6. Mitochondrial Localization
2.2.7. Measurement of Intracellular ROS
2.2.8. Detection of Change in Mitochondria Membrane Potential
2.2.9. Transmission Electron Microscopy
2.2.10. Flow Cytometry
2.2.11. Establishment of the Rat Myocardial Ischemia-Reperfusion Model
2.2.12. Infarct size Determination
2.2.13. Measurement of Left Ventricular Function
2.2.14. Measurements of cTnT, MDA, LDH, SOD Activity and CK-MB
2.2.15. Immunohistochemical Staining
2.2.16. Statistical Analysis
3. Results
3.1. SS31/MSN@PLTM Characterization
3.2. Co-Localization and Cellular ROS Levels
3.3. SS31/MSN@PLTM Maintaining Mitochondrial Membrane Potential and Reducing Apoptosis
3.4. SS31/MSN@PLTM Reducing Myocardial Infarct and Ischemic Sizes and Restoring Cardiac Function
3.5. SS31/MSN@PLTM Maintaining Myocardial Structure and Affecting the Levels of LDH, SOD, MDA, and CK-MB in Rat Serum
3.6. Effects of SS31/MSN@PLTM on the Expression of Apoptosis-Related Proteins
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Yang, M.; Zhang, S.; Ren, S.; Wang, J.; Yun, H.; Yong, S.; Zhang, D.; Yang, Q.; Kou, Y.; Lu, D.; et al. Effect of aqueous extract of sanweitanxiang powder on calcium homeostasis protein expression in ischemic-reperfusion injury rat heart. J. Tradit. Chin. Med. 2013, 33, 355–360. [Google Scholar] [CrossRef] [Green Version]
- Davidson, S.M.; Ferdinandy, P.; Andreadou, I.; Botker, H.E.; Heusch, G.; Ibanez, B.; Ovize, M.; Schulz, R.; Yellon, D.M.; Hausenloy, D.J.; et al. Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. J. Am. Coll. Cardiol. 2019, 73, 89–99. [Google Scholar] [CrossRef] [PubMed]
- Turer, A.T.; Hill, J.A. Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy. Am. J. Cardiol. 2010, 106, 360–368. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cadenas, S. ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection. Free Radic. Biol. Med. 2018, 117, 76–89. [Google Scholar] [CrossRef]
- Shaik, N.F.; Regan, R.F.; Naik, U.P. Platelets as drivers of ischemia/reperfusion injury after stroke. Blood Adv. 2021, 5, 1576–1584. [Google Scholar] [CrossRef]
- Kurian, G.A.; Rajagopal, R.; Vedantham, S.; Rajesh, M. The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited. Oxidative Med. Cell. Longev. 2016, 2016, 1–14. [Google Scholar] [CrossRef] [Green Version]
- Heusch, G.; Boengler, K.; Schulz, R. Inhibition of mitochondrial permeability transition pore opening: The Holy Grail of cardioprotection. Basic Res. Cardiol. 2010, 105, 151–154. [Google Scholar] [CrossRef] [Green Version]
- Wu, D.; Soong, Y.; Zhao, G.-M.; Szeto, H.H. A highly potent peptide analgesic that protects against ischemia-reperfusion-induced myocardial stunning. Am. J. Physiol. Circ. Physiol. 2002, 283, H783–H791. [Google Scholar] [CrossRef] [Green Version]
- Szeto, H.H.; Liu, S.; Soong, Y.; Wu, D.; Darrah, S.F.; Cheng, F.-Y.; Zhao, Z.; Ganger, M.; Tow, C.Y.; Seshan, S.V. Mitochondria-Targeted Peptide Accelerates ATP Recovery and Reduces Ischemic Kidney Injury. J. Am. Soc. Nephrol. 2011, 22, 1041–1052. [Google Scholar] [CrossRef] [Green Version]
- Liu, D.; Shu, G.; Jin, F.; Qi, J.; Xu, X.; Du, Y.; Yu, H.; Wang, J.; Sun, M.; You, Y.; et al. ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule. Sci. Adv. 2020, 6, eabb7422. [Google Scholar] [CrossRef]
- Chen, Y.; Chen, H.; Shi, J. In vivo bio-safety evaluations and diagnostic/therapeutic applications of chemically designed mesoporous silica nanoparticles. Adv. Mater. 2013, 25, 3144–3176. [Google Scholar] [CrossRef] [PubMed]
- Huang, P.; Lian, D.; Ma, H.; Gao, N.; Zhao, L.; Luan, P.; Zeng, X. New advances in gated materials of mesoporous silica for drug controlled release. Chin. Chem. Lett. 2021, 32, 3696–3704. [Google Scholar] [CrossRef]
- Narayan, R.; Nayak, U.Y.; Raichur, A.M.; Garg, S. Mesoporous Silica Nanoparticles: A Comprehensive Review on Synthesis and Recent Advances. Pharmaceutics 2018, 10, 118. [Google Scholar] [CrossRef] [Green Version]
- Beavers, K.R.; Werfel, T.A.; Shen, T.; Kavanaugh, T.E.; Kilchrist, K.V.; Mares, J.W.; Fain, J.S.; Wiese, C.B.; Vickers, K.C.; Weiss, S.M.; et al. Porous Silicon and Polymer Nanocomposites for Delivery of Peptide Nucleic Acids as Anti-MicroRNA Therapies. Adv. Mater. 2016, 28, 7984–7992. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pan, L.; Liu, J.; He, Q.; Shi, J. MSN-mediated sequential vascular-to-cell nuclear-targeted drug delivery for efficient tumor regression. Adv. Mater. 2014, 26, 6742–6748. [Google Scholar] [CrossRef]
- Zhang, T.; Lu, Z.; Wang, J.; Shen, J.; Hao, Q.; Li, Y.; Yang, J.; Niu, Y.; Xiao, Z.; Chen, L.; et al. Preparation of mesoporous silica nanoparticle with tunable pore diameters for encapsulating and slowly releasing eugenol. Chin. Chem. Lett. 2021, 32, 1755–1758. [Google Scholar] [CrossRef]
- Hu, C.-M.J.; Fang, R.H.; Wang, K.-C.; Luk, B.T.; Thamphiwatana, S.; Dehaini, D.; Nguyen, P.; Angsantikul, P.; Wen, C.H.; Kroll, A.V.; et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 2015, 526, 118–121. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gawaz, M. Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium. Cardiovasc. Res. 2004, 61, 498–511. [Google Scholar] [CrossRef]
- Su, T.; Huang, K.; Ma, H.; Liang, H.; Dinh, P.U.; Chen, J.; Shen, D.; Allen, T.A.; Qiao, L.; Li, Z.; et al. Platelet-Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury. Adv. Funct. Mater. 2019, 29, 1803567. [Google Scholar] [CrossRef]
- Wang, S.; Duan, Y.; Zhang, Q.; Komarla, A.; Gong, H.; Gao, W.; Zhang, L. Drug Targeting via Platelet Membrane-Coated Nanoparticles. Small Struct. 2020, 1, 2000018. [Google Scholar] [CrossRef]
- Li, Y.; Teng, X.; Yang, C.; Wang, Y.; Wang, L.; Dai, Y.; Sun, H.; Li, J. Ultrasound Controlled Anti-Inflammatory Polarization of Platelet Decorated Microglia for Targeted Ischemic Stroke Therapy. Angew. Chem. Int. Ed. 2020, 60, 5083–5090. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Li, J.; Chen, J.; Liu, Y.; Cheng, X.; Yang, F.; Gu, N. Platelet Membrane Biomimetic Magnetic Nanocarriers for Targeted Delivery and in Situ Generation of Nitric Oxide in Early Ischemic Stroke. ACS Nano 2020, 14, 2024–2035. [Google Scholar] [CrossRef] [PubMed]
- Flak, D.; Przysiecka, L.; Nowaczyk, G.; Scheibe, B.; Koscinski, M.; Jesionowski, T.; Jurga, S. GQDs-MSNs nanocomposite nanoparticles for simultaneous intracellular drug delivery and fluorescent imaging. J. Nanopart Res. 2018, 20, 306. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, C.-X.; Cheng, Y.; Liu, D.-Z.; Liu, M.; Cui, H.; Zhang, B.-L.; Mei, Q.-B.; Zhou, S.-Y. Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats. J. Nanobiotechnol. 2019, 17, 1–16. [Google Scholar] [CrossRef] [Green Version]
- Xiao, Q.; Dong, X.; Yang, F.; Zhou, S.; Xiang, M.; Lou, L.; Yao, S.Q.; Gao, L. Engineered Cell-Penetrating Peptides for Mitochondrion-Targeted Drug Delivery in Cancer Therapy. Chemistry 2021, 27, 14721–14729. [Google Scholar] [CrossRef]
- Zhao, M.; Wang, Y.; Li, L.; Liu, S.; Wang, C.; Yuan, Y.; Yang, G.; Chen, Y.; Cheng, J.; Lu, Y.; et al. Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance. Theranostics 2021, 11, 1845–1863. [Google Scholar] [CrossRef]
- Chen, D.; Jin, Z.; Zhang, J.; Jiang, L.; Chen, K.; He, X.; Song, Y.; Ke, J.; Wang, Y. HO-1 Protects against Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction in H9c2 Cardiomyocytes. PLoS ONE 2016, 11, e0153587. [Google Scholar] [CrossRef] [Green Version]
- Li, F.; Liu, J.; Tang, S.; Yan, J.; Chen, H.; Li, D.; Yan, X. Quercetin regulates inflammation, oxidative stress, apoptosis, and mitochondrial structure and function in H9C2 cells by promoting PVT1 expression. Acta Histochem. 2021, 123, 151819. [Google Scholar] [CrossRef]
- He, F.; Wu, Q.; Xu, B.; Wang, X.; Wu, J.; Huang, L.; Cheng, J. Suppression of Stim1 reduced intracellular calcium concentration and attenuated hypoxia/reoxygenation induced apoptosis in H9C2 cells. Biosci. Rep. 2017, 37, BSR20171249. [Google Scholar] [CrossRef] [Green Version]
- Nie, C.; Ding, X.; A, R.; Zheng, M.; Li, Z.; Pan, S.; Yang, W. Hydrogen gas inhalation alleviates myocardial ischemia-reperfusion injury by the inhibition of oxidative stress and NLRP3-mediated pyroptosis in rats. Life Sci. 2021, 272, 119248. [Google Scholar] [CrossRef]
- Liu, W.; Chen, C.; Gu, X.; Zhang, L.; Mao, X.; Chen, Z.; Tao, L. AM1241 alleviates myocardial ischemia-reperfusion injury in rats by enhancing Pink1/Parkin-mediated autophagy. Life Sci. 2021, 272, 119228. [Google Scholar] [CrossRef] [PubMed]
- Hong, H.S.; Kim, S.; Lee, S.; Woo, J.S.; Lee, K.H.; Cheng, X.W.; Son, Y.; Kim, W. Substance-P Prevents Cardiac Ischemia-Reperfusion Injury by Modulating Stem Cell Mobilization and Causing Early Suppression of Injury-Mediated Inflammation. Cell. Physiol. Biochem. 2019, 52, 46–56. [Google Scholar]
- Yuan, Y.; Zhai, Y.; Chen, J.; Xu, X.; Wang, H. Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis. Biomolecules 2021, 11, 923. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Wang, X.; Huang, Q.; Li, S.; Zhou, Y.; Li, Z. Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-kappaB pathway in vivo and in vitro. Redox. Biol. 2018, 15, 62–73. [Google Scholar] [CrossRef]
- Xu, J.; Wang, X.; Yin, H.; Cao, X.; Hu, Q.; Lv, W.; Xu, Q.; Gu, Z.; Xin, H. Sequentially Site-Specific Delivery of Thrombolytics and Neuroprotectant for Enhanced Treatment of Ischemic Stroke. ACS Nano 2019, 13, 8577–8588. [Google Scholar] [CrossRef]
- Wang, H.; Wu, J.; Williams, G.R.; Fan, Q.; Niu, S.; Wu, J.; Xie, X.; Zhu, L.-M. Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery. J. Nanobiotechnol. 2019, 17, 1–16. [Google Scholar] [CrossRef]
- Xie, Q.; Zeng, J.; Zheng, Y.; Li, T.; Ren, J.; Chen, K.; Zhang, Q.; Xie, R.; Xu, F.; Zhu, J. Mitochondrial Transplantation Attenuates Cerebral Ischemia-Reperfusion Injury: Possible Involvement of Mitochondrial Component Separation. Oxidative Med. Cell. Longev. 2021, 1006636. [Google Scholar] [CrossRef]
- Cheng, B.; Toh, E.K.W.; Chen, K.-H.; Chang, Y.-C.; Hu, C.-M.J.; Wu, H.-C.; Chau, L.-Y.; Chen, P.; Hsieh, P.C.H. Biomimicking Platelet-Monocyte Interactions as a Novel Targeting Strategy for Heart Healing. Adv. Heal. Mater. 2016, 5, 2686–2697. [Google Scholar] [CrossRef]
- Zhang, X.Y.; Huang, Z.; Li, Q.J.; Zhong, G.Q.; Meng, J.J.; Wang, D.X.; Tu, R.H. Ischemic postconditioning attenuates the inflammatory response in ischemia/reperfusion myocardium by upregulating miR499 and inhibiting TLR2 activation. Mol. Med. Rep. 2020, 22, 209–218. [Google Scholar] [CrossRef]
- Duerr, G.D.; Dewald, D.; Schmitz, E.J.; Verfuerth, L.; Keppel, K.; Peigney, C.; Ghanem, A.; Welz, A.; Dewald, O. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice. Mediators Inflamm. 2016, 2016, 7174127. [Google Scholar] [CrossRef] [Green Version]
- Rawat, D.K.; Hecker, P.; Watanabe, M.; Chettimada, S.; Levy, R.J.; Okada, T.; Edwards, J.G.; Gupte, S.A. Glucose-6-Phosphate Dehydrogenase and NADPH Redox Regulates Cardiac Myocyte L-Type Calcium Channel Activity and Myocardial Contractile Function. PLoS ONE 2012, 7, e45365. [Google Scholar] [CrossRef] [PubMed]
- Zhao, H.; Yenari, M.A.; Cheng, D.; Sapolsky, R.M.; Steinberg, G.K. Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. J. Neurochem. 2003, 85, 1026–1036. [Google Scholar] [CrossRef] [PubMed]
- Sun, H.; Lv, C.; Yang, L.; Wang, Y.; Zhang, Q.; Yu, S.; Kong, H.; Wang, M.; Xie, J.; Zhang, C.; et al. Solanine induces mitochondria-mediated apoptosis in human pancreatic cancer cells. Biomed. Res. Int. 2014, 2014, 805926. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, C.; Yang, X.; Jiang, Y.; Qi, L.; Zhuge, D.; Xu, T.; Guo, Y.; Deng, M.; Zhang, W.; Tian, D.; et al. Targeted delivery of fat extract by platelet membrane-cloaked nanocarriers for the treatment of ischemic stroke. J. Nanobiotechnol. 2022, 20, 249. [Google Scholar] [CrossRef]
- Xu, L.; Gao, F.; Fan, F.; Yang, L. Platelet membrane coating coupled with solar irradiation endows a photodynamic nanosystem with both improved antitumor efficacy and undetectable skin damage. Biomaterials 2018, 159, 59–67. [Google Scholar] [CrossRef]
- Bruno, B.J.; Miller, G.D.; Lim, C.S. Basics and recent advances in peptide and protein drug delivery. Ther. Deliv. 2013, 4, 1443–1467. [Google Scholar] [CrossRef] [Green Version]
- Zhao, W.-Y.; Han, S.; Zhang, L.; Zhu, Y.-H.; Wang, L.-M.; Zeng, L. Mitochondria-Targeted Antioxidant Peptide SS31 Prevents Hypoxia/Reoxygenation-Induced Apoptosis by Down-Regulating p66Shc in Renal Tubular Epithelial Cells. Cell. Physiol. Biochem. 2013, 32, 591–600. [Google Scholar] [CrossRef]
- Shen, R.; Zhou, J.; Li, G.; Chen, W.; Zhong, W.; Chen, Z. SS31 attenuates oxidative stress and neuronal apoptosis in early brain injury following subarachnoid hemorrhage possibly by the mitochondrial pathway. Neurosci. Lett. 2019, 717, 134654. [Google Scholar] [CrossRef]
- Grosser, J.A.; Fehrman, R.L.; Keefe, D.; Redmon, M.; Nickells, R.W. The effects of a mitochondrial targeted peptide (elamipretide/SS31) on BAX recruitment and activation during apoptosis. BMC Res. Notes 2021, 14, 198. [Google Scholar] [CrossRef]
- Birk, A.V.; Liu, S.; Soong, Y.; Mills, W.; Singh, P.; Warren, J.D.; Seshan, V.; Pardee, J.D.; Szeto, H.H. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J. Am. Soc. Nephrol. 2013, 24, 1250–1261. [Google Scholar] [CrossRef] [Green Version]
- Cory, S.; Adams, J.M. The Bcl2 family: Regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2002, 2, 647–656. [Google Scholar] [CrossRef] [PubMed]
- Gómez-Crisóstomo, N.P.; López-Marure, R.; Zapata, E.; Zazueta, C.; Martínez-Abundis, E. Bax induces cytochrome c release by multiple mechanisms in mitochondria from MCF7 cells. J. Bioenerg. Biomembr. 2013, 45, 441–448. [Google Scholar] [CrossRef] [PubMed]
- Boatright, K.M.; Salvesen, G.S. Mechanisms of caspase activation. Curr. Opin. Cell Biol. 2003, 15, 725–731. [Google Scholar] [CrossRef]
- Pena-Blanco, A.; Garcia-Saez, A.J. Bax, Bak and beyond—Mitochondrial performance in apoptosis. FEBS J. 2018, 285, 416–431. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Culmsee, C.; Zhu, C.; Landshamer, S.; Becattini, B.; Wagner, E.; Pellecchia, M.; Blomgren, K.; Plesnila, N. Apoptosis-Inducing Factor Triggered by Poly (ADP-Ribose) Polymerase and Bid Mediates Neuronal Cell Death after Oxygen-Glucose Deprivation and Focal Cerebral Ischemia. J. Neurosci. 2005, 25, 10262–10272. [Google Scholar] [CrossRef]
0 h | 1 h | 3 h | 6 h | 12 h | 24 h | |
---|---|---|---|---|---|---|
Particle size(nm) | 80.84 ± 3.17 | 84.75 ± 4.60 | 83.56 ± 3.39 | 83.55 ± 3.10 | 86.43 ± 3.67 | 84.79 ± 3.64 |
Zeta potential (mV) | −1.35 ± 0.12 | −1.26 ± 0.17 | −1.1 ± 0.25 | −1.14 ± 0.40 | −1.06 ± 0.32 | −1.23 ± 0.29 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhang, Z.; Chen, Z.; Yang, L.; Zhang, J.; Li, Y.; Li, C.; Wang, R.; Wang, X.; Huang, S.; Hu, Y.; et al. Platelet Membrane–Encapsulated MSNs Loaded with SS31 Peptide Alleviate Myocardial Ischemia-Reperfusion Injury. J. Funct. Biomater. 2022, 13, 181. https://doi.org/10.3390/jfb13040181
Zhang Z, Chen Z, Yang L, Zhang J, Li Y, Li C, Wang R, Wang X, Huang S, Hu Y, et al. Platelet Membrane–Encapsulated MSNs Loaded with SS31 Peptide Alleviate Myocardial Ischemia-Reperfusion Injury. Journal of Functional Biomaterials. 2022; 13(4):181. https://doi.org/10.3390/jfb13040181
Chicago/Turabian StyleZhang, Zaiyuan, Zhong Chen, Ling Yang, Jian Zhang, Yubo Li, Chengming Li, Rui Wang, Xue Wang, Shuo Huang, Yonghe Hu, and et al. 2022. "Platelet Membrane–Encapsulated MSNs Loaded with SS31 Peptide Alleviate Myocardial Ischemia-Reperfusion Injury" Journal of Functional Biomaterials 13, no. 4: 181. https://doi.org/10.3390/jfb13040181