Cationic CaMKII Inhibiting Nanoparticles Prevent Allergic Asthma
Open accessAbstract
Asthma is a common lung disease affecting over 300 million people worldwide and is associated with increased reactive oxygen species, eosinophilic airway inflammation, bronchoconstriction, and mucus production. Targeting of novel therapeutic agents to the lungs of patients with asthma may improve efficacy of treatments and minimize side effects. We previously demonstrated that Ca 2+ /calmodulin-dependent protein kinase (CaMKII) is expressed and activated in the bronchial epithelium of asthmatic patients. CaMKII inhibition in murine models of allergic asthma reduces key disease phenotypes, providing the rationale for targeted CaMKII inhibition as a potential therapeutic approach for asthma. Herein we developed a novel cationic nanoparticle (NP)-based system for delivery of the potent and specific CaMKII inhibitor peptide, CaMKIIN, to airways.1 CaMKIIN-loaded NPs abrogated the severity of allergic asthma in a murine model. These findings provide the basis for development of innovative, site-specific drug delivery therapies, particularly for treatment of pulmonary diseases such as asthma.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CaMKIIN-loaded NPs mitigated severity of allergic asthma in mouse model.
“CaMKII inhibitor peptide (CaMKIIN)-loaded NPs mitigated the severity of allergic asthma in a mouse model.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [175]
Nanosized chitosan-coated PLGA NPs sustain release of CaMKIIN with effective cellular uptake.
“Nanosized chitosan-coated PLGA NPs were reported to have the ability to sustain the release of CaMKIIN with effective cellular uptake (Fig. 7a–c).”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [175]
Chitosan-coated NPs specifically localize in lungs and fluoresce up to 48 h, suggesting release of CaMKIIN with higher bioavailability and high retention time.
“These chitosan-coated NPs specifically localize in the lungs and fluoresce up to 48 h, which suggests that NPs are able to release CaMKIIN with higher bioavailability and high retention time (Fig. 7e, f).175”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [175]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
Chung, K. F., Wenzel, S. E., Brozek, J. L., Bush, A., Castro, M., Sterk, P. J., Adcock, I. M., Bateman, E. D., Bel, E. H., Bleecker, E. R., et al. (2014) · European Respiratory Journal · doi:10.1183/09031936.00202013 · Cited by 3,926 · see citing works
Passage of inhaled particles into the blood circulation in humans
Nemmar, A., Hoet, P. H. M., Vanquickenborne, B., Dinsdale, D., Thomeer, M., Hoylaerts, M. F., Vanbilloen, H., Mortelmans, L., & Nemery, B. (2002) · Circulation · doi:10.1161/hc0402.104118 · Cited by 1,719 · see citing works
A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation
Erickson, J. R., Joiner, M.-L. A., Guan, X., Kutschke, W., Yang, J., Oddis, C. V., Bartlett, R. K., Lowe, J. S., O'Donnell, S. E., Aykin-Burns, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.02.048 · Cited by 1,122 · see citing works
Self-citationPanyam, J., Zhou, W., Prabha, S., Sahoo, S. K., & Labhasetwar, V. D. (2002) · The FASEB Journal · doi:10.1096/fj.02-0088com · Cited by 1,044 · see citing works
Effect of Chitosan on the Permeability of Monolayers of Intestinal Epithelial Cells (Caco-2)
Artursson, P., Lindmark, T., Davis, S. S., & Illum, L. (1994) · Pharmaceutical Research · doi:10.1023/a:1018967116988 · Cited by 766 · see citing works
Pulmonary and Systemic Distribution of Inhaled Ultrafine Silver Particles in Rats
Takenaka, S., Karg, E. W., Roth, C., Schulz, H., Ziesenis, A., Heinzmann, U., Schramel, P., & Heyder, J. (2001) · Environmental Health Perspectives · doi:10.1289/ehp.01109s4547 · Cited by 731 · see citing works
Mahapatro, A., & Singh, D. K. (2011) · Journal of Nanobiotechnology · doi:10.1186/1477-3155-9-55 · Cited by 685 · see citing works
Toxicity of Nanoparticles and an Overview of Current Experimental Models.
Bahadar, H., Maqbool, F., Niaz, K., & Abdollahi, M. R. (2016) · PubMed Central · doi:10.7508/ibj.2016.01.001 · Cited by 645 · see citing works
What do we (need to) know about the kinetic properties of nanoparticles in the body?
Hagens, W. I., Oomen, A. G., de Jong, W. H., Cassee, F. R., & Sips, A. J. A. M. (2007) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2007.07.006 · Cited by 463 · see citing works
Steinke, J. W., & Borish, L. (2001) · Respiratory Research · doi:10.1186/rr40 · Cited by 445 · see citing works
You, Y., Richer, E. J., Huang, T., & Brody, S. L. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00169.2002 · Cited by 442 · see citing works
Karp, P. H., Moninger, T. O., Weber, S. P., Nesselhauf, T. S., Launspach, J. L., Zabner, J., & Welsh, M. J. (2003) · Humana Press eBooks · doi:10.1385/1-59259-185-x:115 · Cited by 345 · see citing works
The future of drug safety testing: expanding the view and narrowing the focus
Stevens, J. L., & Baker, T. K. (2009) · Drug Discovery Today · doi:10.1016/j.drudis.2008.11.009 · Cited by 286 · see citing works
Mucus hypersecretion in asthma: causes and effects
Evans, C. M., Kim, K., Tuvim, M. J., & Dickey, B. F. (2008) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e32831da8d3 · Cited by 282 · see citing works
Design of Nanoparticle-Based Carriers for Targeted Drug Delivery
Yu, X., Trase, I., Ren, M., et al. (2016) · Journal of Nanomaterials · doi:10.1155/2016/1087250 · Cited by 266 · see citing works
Asthma: pathogenesis and novel drugs for treatment
Olin, J. T., & Wechsler, M. E. (2014) · BMJ · doi:10.1136/bmj.g5517 · Cited by 254 · see citing works
Systemic delivery of siRNA with cationic lipid assisted PEG-PLA nanoparticles for cancer therapy
Yang, X., Dou, S., Sun, T., Mao, C., Wang, H., & Wang, J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.07.035 · Cited by 242 · see citing works
Nanotechnology: What it can do for drug delivery
Park, K. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.05.003 · Cited by 240 · see citing works
Biodegradable Particles as Vaccine Delivery Systems: Size Matters
Joshi, V. B., Geary, S. M., & Salem, A. K. (2012) · The AAPS Journal · doi:10.1208/s12248-012-9418-6 · Cited by 233 · see citing works
Self-citationCharacterization of a calmodulin kinase II inhibitor protein in brain
Chang, B. H., Mukherji, S., & Soderling, T. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10890 · Cited by 227 · see citing works
Role of Interleukin-13 in Asthma
Corren, J. (2013) · Current Allergy and Asthma Reports · doi:10.1007/s11882-013-0373-9 · Cited by 203 · see citing works
Eotaxin and the attraction of eosinophils to the asthmatic lung
Conroy, D. M., & Williams, T. J. (2001) · Respiratory Research · doi:10.1186/rr52 · Cited by 199 · see citing works
New therapies for asthma: is there any progress?
Barnes, P. J. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.04.009 · Cited by 191 · see citing works
Lakatos, H. F., Burgess, H. A., Thatcher, T. H., Redonnet, M. R., Hernady, E., Williams, J. P., & Sime, P. J. (2006) · Experimental Lung Research · doi:10.1080/01902140600817465 · Cited by 176 · see citing works
Chitosan-based systems for the delivery of vaccine antigens
Arca, H. Ç., Günbeyaz, M., & Şenel, S. (2009) · Expert Review of Vaccines · doi:10.1586/erv.09.47 · Cited by 167 · see citing works
Pope, S. M., Fulkerson, P. C., Blanchard, C., Akei, H. S., Nikolaidis, N. M., Zimmermann, N., Molkentin, J. D., & Rothenberg, M. E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m406037200 · Cited by 157 · see citing works
CaMKII oxidative activation and the pathogenesis of cardiac disease
Luczak, E. D., & Anderson, M. E. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.02.004 · Cited by 153 · see citing works
Self-citationHouse dust mite–induced asthma causes oxidative damage and DNA double-strand breaks in the lungs
Chan, T. K., Loh, X. Y., Peh, H. Y., Tan, W. N. F., Tan, W. S. D., Li, N., Tay, I. J. J., Wong, W. S. F., & Engelward, B. P. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.02.017 · Cited by 143 · see citing works
Householder, K. T., DiPerna, D. M., Chung, E. P., Wohlleb, G. M., Dhruv, H., Berens, M. E., & Sirianni, R. W. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.01.002 · Cited by 129 · see citing works
Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles
Guo, C., & Gemeinhart, R. A. (2008) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.06.008 · Cited by 129 · see citing works
Oh, Y. J., Lee, J., Seo, J. Y., Rhim, T., Kim, S., Yoon, H. J., & Lee, K. Y. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.001 · Cited by 118 · see citing works
Pease, J. E. (2001) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(01)00044-3 · Cited by 111 · see citing works
Oxidant stress promotes disease by activating CaMKII
Anderson, M. E. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.10.014 · Cited by 109 · see citing works
Self-citationActivation of CaMKII as a key regulator of reactive oxygen species production in diabetic rat heart
Nishio, S., Teshima, Y., Takahashi, N., Thuc, L. C., Saito, S., Fukui, A., Kume, O., Fukunaga, N., Hara, M., Nakagawa, M., et al. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2012.02.006 · Cited by 96 · see citing works
Worthington, K. S., Adamcakova‐Dodd, A., Wongrakpanich, A., et al. (2013) · Nanotechnology · doi:10.1088/0957-4484/24/39/395101 · Cited by 80 · see citing works
Self-citationLu, J., Chuan, X., Zhang, H., Dai, W., Wang, X., Wang, X., & Zhang, Q. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.05.032 · Cited by 70 · see citing works
Youn, Y. S., Choi, J. S., Lee, C., Kim, I.-S., Oh, K. T., Lee, Lee, K. C., & Park, E. (2013) · International Journal of Nanomedicine · doi:10.2147/ijn.s48197 · Cited by 63 · see citing works
CaMKII Is Essential for the Proasthmatic Effects of Oxidation
Sanders, P. N., Koval, O. M., Jaffer, O. A., Prasad, A. M., Businga, T. R., Scott, J. A., Hayden, P. J., Luczak, E. D., Dickey, D. D., Allamargot, C., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006135 · Cited by 62 · see citing works
Self-citationEffects of Caryota mitis profilin-loaded PLGA nanoparticles in a murine model of allergic asthma
Mei, L., Zeng, X., Liu, Z., Zhang, X., Ma, L., Xiao, X., Liu, X., & Yu, H. (2013) · International Journal of Nanomedicine · doi:10.2147/ijn.s51633 · Cited by 53 · see citing works
Shalaby, K. H., Allard-Coutu, A., O’Sullivan, M. J., Nakada, E. M., Qureshi, S. T., Day, B. J., & Martin, J. G. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1103644 · Cited by 44 · see citing works
Role of CaMKII and ROS in rapid pacing-induced apoptosis
Sepúlveda, M., Gonano, L. A., Back, T. G., et al. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.07.013 · Cited by 42 · see citing works
Oxidized CaMKII promotes asthma through the activation of mast cells
Qu, J., Do, D. C., Zhou, Y., Luczak, E. D., Mitzner, W., Anderson, M. E., & Gao, P. (2017) · JCI Insight · doi:10.1172/jci.insight.90139 · Cited by 42 · see citing works
Self-citationZhu, L. J., Klutho, P. J., Scott, J. A., Xie, L., Luczak, E. D., Dibbern, M. E., Prasad, A. M., Jaffer, O. A., Venema, A. N., Nguyen, E. K., et al. (2014) · Vascular Pharmacology · doi:10.1016/j.vph.2014.01.001 · Cited by 36 · see citing works
Self-citationHoda, M., Pajaniradje, S., Shakya, G., Mohankumar, K., & Rajagopalan, R. (2016) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2016.02.013 · Cited by 35 · see citing works
Scott, J. A., Klutho, P. J., Accaoui, R. N. E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071550 · Cited by 21 · see citing works
Lemke-Miltner, C. D., Graham, J. B., Geary, S. M., et al. (2011) · Molecular Pharmaceutics · doi:10.1021/mp100464y · Cited by 12 · see citing works
Stress Response Signaling Pathways May Lead to Mitochondrial Biogenesis
Luo, M., & Joiner, M.-L. A. (2014) · Diabetes · doi:10.2337/db14-0373 · Cited by 9 · see citing works
Chung, K. F., Wenzel, S. E., Brożek, J., et al. (2014) · European Respiratory Journal · doi:10.1183/09031936.50202013 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles
Singh, A. P., Biswas, A., Shukla, A., & Maiti, P. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0068-3 · Cited by 645 · see citing works
- Authors
- Morris, A. S., Sebag, S. C., Paschke, J. D., Wongrakpanich, A., Ebeid, K., Anderson, M. E., Grumbach, I. M., & Salem, A. K.
- Affiliations
- University of Iowa (US)
- Mahidol University (TH)
- Johns Hopkins University (US)
- Corresponding author
- Grumbach, Isabella M.
- Salem, Aliasger K.
- ORCID
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-05-09
- Volume
- 14
- Issue
- 6
- Pages
- 2166-2175
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC5800301
- OpenAlex
- W2610827450
- Cited by
- 27
- References
- 48
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 3
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (P30 ES005605, U01 ES027252 01)
- National Institute of Dental and Craniofacial Research
- College of Pharmacy, University of Iowa
- Roy J. and Lucille A. Carver College of Medicine, University of Iowa
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- allergic asthma, CaMKII inhibition, cationic nanoparticles, bronchial epithelium, eosinophilic airway inflammation, pulmonary drug delivery, murine asthma model
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Asthma, Lung, Polyglycolic Acid, Drug Delivery Systems, Lactic Acid, Mice, Nanoparticles, Calcium-Calmodulin-Dependent Protein Kinase Type 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
