Novel cystamine-core dendrimer-formulation rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection by augmenting autophagy

References

• Luciani A, Villella VR, Esposito S, et al. Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat Cell Biol. 2010;12(9):863–875. PubMed PMID: 20711182.
   PubMed Web of Science ®Google Scholar
• Scotet V, Duguépéroux I, Saliou P, et al. Evidence for decline in the incidence of cystic fibrosis: a 35-year observational study in Brittany, France. Orphanet J Rare Dis. 2012;7:14. Epub 2012/03/01. PubMed PMID: 22380742; PubMed Central PMCID: PMCPMC3310838. .
   PubMed Web of Science ®Google Scholar
• De Stefano D, Villella VR, Esposito S, et al. Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation. Autophagy . 2014;10(11):2053–2074. PubMed PMID: 25350163; PubMed Central PMCID: PMCPMC4502695. .
   PubMed Web of Science ®Google Scholar
• Lukacs GL, Verkman AS. CFTR: folding, misfolding and correcting the DeltaF508 conformational defect. Trends Mol Med. 2012;18(2):81–91. PubMed PMID: 22138491; PubMed Central PMCID: PMCPMC3643519
   PubMed Web of Science ®Google Scholar
• Ferrari E, Monzani R, Villella VR, et al. Cysteamine re-establishes the clearance of Pseudomonas aeruginosa by macrophages bearing the cystic fibrosis-relevant F508del-CFTR mutation. Cell Death Dis. 2017;8(1):e2544. PubMed PMID: 28079883.
   PubMedGoogle Scholar
• Ratjen F, Döring G. Cystic fibrosis. Lancet. 2003;361(9358):681–689. PubMed PMID: 12606185
   PubMed Web of Science ®Google Scholar
• Charrier C, Rodger C, Robertson J, et al. Cysteamine (Lynovex(R)), a novel mucoactive antimicrobial & antibiofilm agent for the treatment of cystic fibrosis. Orphanet J Rare Dis. 2014;9:189. PubMed PMID: 25433388; PubMed Central PMCID: PMCPMC4260250.
   PubMed Web of Science ®Google Scholar
• Ehrhardt C, Collnot EM, Baldes C, et al. Towards an in vitro model of cystic fibrosis small airway epithelium: characterisation of the human bronchial epithelial cell line CFBE41o. Cell Tissue Res. 2006;323(3):405–415. PubMed PMID: 16249874.
   PubMed Web of Science ®Google Scholar
• Bodas M, Min T, Mazur S, et al. Critical modifier role of membrane-cystic fibrosis transmembrane conductance regulator-dependent ceramide signaling in lung injury and emphysema. J Immunol. 2011;186(1):602–613. Epub 2010/12/08. PubMed PMID: 21135173; PubMed Central PMCID: PMC3119853.
   PubMed Web of Science ®Google Scholar
• Clunes LA, Davies CM, Coakley RD, et al. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. FASEB J. 2012;26(2):533–545. PubMed PMID: 21990373; PubMed Central PMCID: PMCPMC3290447.
   PubMed Web of Science ®Google Scholar
• Ni I, Ji C, Vij N. Second-hand cigarette smoke impairs bacterial phagocytosis in macrophages by modulating CFTR dependent lipid-rafts. PLoS One. 2015;10(3):e0121200. PubMed PMID: 25794013; PubMed Central PMCID: PMCPMC4368805
   PubMed Web of Science ®Google Scholar
• Luciani A, Villella VR, Esposito S, et al. Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on DeltaF508 cystic fibrosis transmembrane conductance regulator. Autophagy. 2012;8(11):1657–1672. PubMed PMID: 22874563; PubMed Central PMCID: PMCPMC3494594.
   PubMed Web of Science ®Google Scholar
• Ferreira AG, Leao RS, Carvalho-Assef AP, et al. Low-level resistance and clonal diversity of Pseudomonas aeruginosa among chronically colonized cystic fibrosis patients. APMIS. 2015;123(12):1061–1068. PubMed PMID: 26522829.
   PubMed Web of Science ®Google Scholar
• Vij N, Min T, Marasigan R, et al. Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis. J Nanobiotechnology. 2010;8:22. PubMed PMID: 20868490; PubMed Central PMCID: PMCPMC2954907.
   PubMedGoogle Scholar
• Deacon J, Abdelghany SM, Quinn DJ, et al. Antimicrobial efficacy of tobramycin polymeric nanoparticles for Pseudomonas aeruginosa infections in cystic fibrosis: formulation, characterisation and functionalisation with dornase alfa (DNase). J Control Release. 2015;198:55–61. PubMed PMID: 25481442.
   PubMed Web of Science ®Google Scholar
• Stanton BA, Coutermarsh B, Barnaby R, et al. Pseudomonas aeruginosa reduces VX-809 stimulated F508del-CFTR chloride secretion by airway epithelial cells. PLoS One. 2015;10(5):e0127742. PubMed PMID: 26018799; PubMed Central PMCID: PMCPMC4446214
   PubMed Web of Science ®Google Scholar
• Moreau-Marquis S, Redelman CV, Stanton BA, et al. Co-culture models of Pseudomonas aeruginosa biofilms grown on live human airway cells. J Vis Exp. 2010;(44). PubMed PMID: 20972407; PubMed Central PMCID: PMCPMC3185622. DOI:10.3791/2186
   PubMedGoogle Scholar
• Joseph T, Look D, Ferkol T. NF-kappaB activation and sustained IL-8 gene expression in primary cultures of cystic fibrosis airway epithelial cells stimulated with Pseudomonas aeruginosa. Am J Physiol Lung Cell Mol Physiol. 2005;288(3):L471–9. PubMed PMID: 15516493
   PubMed Web of Science ®Google Scholar
• Junkins RD, McCormick C, Lin TJ. The emerging potential of autophagy-based therapies in the treatment of cystic fibrosis lung infections. Autophagy. 2014;10(3):538–547. Epub 2014/01/13. PubMed PMID: 24434788; PubMed Central PMCID: PMCPMC4077897.
   PubMed Web of Science ®Google Scholar
• Besouw M, Masereeuw R, van den Heuvel L, et al. Cysteamine: an old drug with new potential. Drug Discov Today. 2013;18(15–16):785–792. PubMed PMID: 23416144
   PubMed Web of Science ®Google Scholar
• Kobes JE, Daryaei I, Howison CM, et al. Improved treatment of pancreatic cancer with drug delivery nanoparticles loaded with a novel AKT/PDK1 inhibitor. Pancreas. 2016;45(8):1158–1166. PubMed PMID: 26918875; PubMed Central PMCID: PMCPMC4983222.
   PubMed Web of Science ®Google Scholar
• Vij N, Nano-based rescue of dysfunctional autophagy in chronic obstructive lung diseases. Expert Opin Drug Deliv. 2016; 1–7. PubMed PMID: 27561233. DOI:10.1080/17425247.2016.1223040.
   Web of Science ®Google Scholar
• Vu CB, Bridges RJ, Pena-Rasgado C, et al. Fatty acid cysteamine conjugates as novel and potent autophagy activators that enhance the correction of misfolded F508del-cystic fibrosis transmembrane conductance regulator (CFTR). J Med Chem. 2017;60(1):458–473. PubMed PMID: 27976892.
   PubMed Web of Science ®Google Scholar
• Yang H. Targeted nanosystems: advances in targeted dendrimers for cancer therapy. Nanomedicine. 2016;12(2):309–316. PubMed PMID: 26706410; PubMed Central PMCID: PMCPMC4789125
   PubMed Web of Science ®Google Scholar
• Kannan RM, Nance E, Kannan S, et al. Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J Intern Med. 2014;276(6):579–617. PubMed PMID: 24995512
   PubMed Web of Science ®Google Scholar
• Brockman SM, Bodas M, Silverberg D, et al. Dendrimer-based selective autophagy-induction rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection in cystic fibrosis. PLoS One. 2017;12(9):e0184793. Epub 2017/09/13. PubMed PMID: 28902888; PubMed Central PMCID: PMCPMC5597233.
   PubMed Web of Science ®Google Scholar
• Sharma A, Desai A, Ali R, et al. Polyacrylamide gel electrophoresis separation and detection of polyamidoamine dendrimers possessing various cores and terminal groups. J Chromatogr A. 2005;1081(2): 238–244. PubMed PMID: 16038215.
   PubMed Web of Science ®Google Scholar
• Upadhaya SK, Swanson DR, Tomalia DA, et al. Analysis of polyamidoamine dendrimers by isoelectric focusing. Anal Bioanal Chem. 2014;406(2):455–458. Epub 2013/11/19. PubMed PMID: 24247550.
   PubMed Web of Science ®Google Scholar
• Vij N, Fang S, Zeitlin PL. Selective inhibition of endoplasmic reticulum-associated degradation rescues DeltaF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels: therapeutic implications. J Biol Chem. 2006;281(25):17369–17378. PubMed PMID: 16621797
   PubMed Web of Science ®Google Scholar
• Brill SR, Ross KE, Davidow CJ, et al. Immunolocalization of ion transport proteins in human autosomal dominant polycystic kidney epithelial cells. Proc Natl Acad Sci U S A. 1996;93(19): 10206–10211. PubMed PMID: 8816777; PubMed Central PMCID: PMCPMC38362.
   PubMed Web of Science ®Google Scholar
• Crawford I, Maloney PC, Zeitlin PL, et al. Immunocytochemical localization of the cystic fibrosis gene product CFTR. Proc Natl Acad Sci U S A. 1991;88(20):9262–9266. PubMed PMID: 1718002; PubMed Central PMCID: PMCPMC52694.
   PubMed Web of Science ®Google Scholar
• Shivalingappa PC, Hole R, Westphal CV, et al. Airway exposure to e-cigarette vapors impairs autophagy and induces aggresome formation. Antioxid Redox Signal. 2015. PubMed PMID: 26377848; PubMed Central PMCID: PMCPMC4744882. DOI:10.1089/ars.2015.6367
   PubMed Web of Science ®Google Scholar
• Bodas M, Silverberg D, Walworth K, et al. Augmentation of S-nitrosoglutathione (GSNO) controls cigarette-smoke induced inflammatory-oxidative stress and COPD-emphysema pathogenesis by restoring CFTR function. Antioxid Redox Signal. 2016. PubMed PMID: 28006950. DOI:10.1089/ars.2016.6895
   Web of Science ®Google Scholar
• Bodas M, Patel N, Silverberg D, et al. Master autophagy regulator Transcription factor-EB (TFEB) regulates cigarette smoke induced autophagy-impairment and COPD-emphysema pathogenesis. Antioxid Redox Signal. 2016. PubMed PMID: 27835930. DOI:10.1089/ars.2016.6842
   Web of Science ®Google Scholar
• Bodas M, Min T, Vij N. Lactosylceramide-accumulation in lipid-rafts mediate aberrant-autophagy, inflammation and apoptosis in cigarette smoke induced emphysema. Apoptosis. 2015;20:725–739. Epub 2015/02/02. PubMed PMID: 25638276.
   PubMed Web of Science ®Google Scholar
• Bodas M, Van Westphal C, Carpenter-Thompson R, et al. Nicotine exposure induces bronchial epithelial cell apoptosis and senescence via ROS mediated autophagy-impairment. Free Radic Biol Med. 2016;97:441–453. PubMed PMID: 27394171.
   PubMed Web of Science ®Google Scholar
• Villella VR, Esposito S, Bruscia EM, et al. Targeting the intracellular environment in cystic fibrosis: restoring autophagy as a novel strategy to circumvent the CFTR defect. Front Pharmacol. 2013;4:1. PubMed PMID: 23346057; PubMed Central PMCID: PMCPMC3549520
   PubMed Web of Science ®Google Scholar
• Villella VR, Esposito S, Bruscia EM, et al. Disease-relevant proteostasis regulation of cystic fibrosis transmembrane conductance regulator. Cell Death Differ. 2013;20(8):1101–1115. Epub 2013/05/17. PubMed PMID: 23686137; PubMed Central PMCID: PMCPMC3705602
   PubMed Web of Science ®Google Scholar
• Today CFN. First patients dosed in phase 2 test of lynovex for CF exacerbations 2015. [cited 2018 Sep 11]. Available from: https://cysticfibrosisnewstoday.com/2017/01/19/novabiotics-announces-first-cystic-fibrosis-patients-dosed-in-lynovex-clinical-study/
   Google Scholar
• Junkins RD, Shen A, Rosen K, et al. Autophagy enhances bacterial clearance during P. aeruginosa lung infection. PLoS One. 2013;8(8):e72263. PubMed PMID: 24015228; PubMed Central PMCID: PMCPMC3756076
   PubMed Web of Science ®Google Scholar
• Vij N. Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential. Expert Opin Drug Deliv. 2011;8(9):1105–1109. PubMed PMID: 21711085; PubMed Central PMCID: PMCPMC3159857
   PubMed Web of Science ®Google Scholar
• Roy I, Vij N. Nanodelivery in airway diseases: challenges and therapeutic applications. Nanomedicine. 2010;6(2):237–244. PubMed PMID: 19616124; PubMed Central PMCID: PMCPMC2847663
   PubMed Web of Science ®Google Scholar