Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier

Pulmonary Pharmacology and Therapeutics

Volumn 34, Issue , 2015, Pages 8-24

  Di Gioia, Sante ^a   Trapani, Adriana ^b   Castellani, Stefano ^a   Carbone, Annalucia ^a,c   Belgiovine, Giuliana ^a   Craparo, Emanuela Fabiola ^d   Puglisi, Giovanni ^e   Cavallaro, Gennara ^d   Trapani, Giuseppe ^b   Conese, Massimo ^a  

^a UNIVERSITY OF FOGGIA   (Italy)

^b UNIVERSITY OF BARI   (Italy)

^c FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

^d UNIVERSITY OF PALERMO   (Italy)

^e UNIVERSITY OF CATANIA   (Italy)

Author keywords

Asthma; Cystic fibrosis; Lung cancer; Mucolytics; Poly(ethylene glycol); Sputum

Indexed keywords

LIPID; MACROGOL; MUCOLYTIC AGENT; NANOCOMPLEX; NANOPARTICLE; POLYMER; UNCLASSIFIED DRUG; AUTACOID; EXPECTORANT AGENT; MACROGOL DERIVATIVE; SMALL INTERFERING RNA;

ALLERGIC ASTHMA; ARTICLE; BIOCHEMISTRY; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL (TOPIC); CYSTIC FIBROSIS; GENE EXPRESSION; GENE TRANSFER; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; LUNG ALVEOLUS CELL; LUNG CANCER; MUCUS; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; NONVIRAL GENE THERAPY; PRIORITY JOURNAL; RESPIRATORY EPITHELIUM; RESPIRATORY FUNCTION; RESPIRATORY TRACT DISEASE; ADMINISTRATION AND DOSAGE; CHEMISTRY; GENE THERAPY; LUNG; METABOLISM; PHARMACEUTICS; PLASMID; PROCEDURES;

CYSTIC FIBROSIS; EXPECTORANTS; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; LUNG; MUCUS; NANOPARTICLES; PLASMIDS; POLYETHYLENE GLYCOLS; RNA, SMALL INTERFERING; TECHNOLOGY, PHARMACEUTICAL;

EID: 84943268784     PISSN: 10945539     EISSN: 15229629     Source Type: Journal    
DOI: 10.1016/j.pupt.2015.07.003     Document Type: Article

References (170)

1. Aneja M.K., Geiger J.P., Himmel A., Rudolph C. Targeted gene delivery to the lung. Expert Opin. Drug Deliv. 2009, 6:567-583.
2. Griesenbach U., Alton E.W. Gene transfer to the lung: lessons learned from more than 2 decades of CF gene therapy. Adv. Drug Deliv. Rev. 2009, 61:128-139.
3. Kaur G., Narang R.K., Rath G., Goyal A.K. Advances in pulmonary delivery of nanoparticles. Artif. Cells Blood Substit. Immobil. Biotechnol. 2012, 40:75-96.
4. Geiger J., Aneja M.K., Rudolph C. Vectors for pulmonary gene therapy. Int. J. Pharm. 2010, 390:84-88.
5. Yu J., Chien Y.W. Pulmonary drug delivery: physiologic and mechanistic aspects. Crit. Rev. Ther. Drug Carr. Syst. 1997, 14:395-453.
6. McWilliam A.S., Holt P.G. Immunobiology of dendritic cells in the respiratory tract: steady-state and inflammatory sentinels?. Toxicol. Lett. 1998, 102-103:323-329.
7. Thornton D.J., Sheehan J.K. From mucins to mucus: toward a more coherent understanding of this essential barrier. Proc. Am. Thorac. Soc. 2004, 1:54-61.
8. Cone R.A. Barrier properties of mucus. Adv. Drug Deliv. Rev. 2009, 61:75-85.
9. Voynow J.A., Rubin B.K. Mucins, mucus, and sputum. Chest 2009, 135:505-512.
10. Lai S.K., O'Hanlon D.E., Harrold S., Man S.T., Wang Y.Y., Cone R., et al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:1482-1487.
11. Lai S.K., Wang Y.Y., Wirtz D., Hanes J. Micro- and macrorheology of mucus. Adv. Drug Deliv. Rev. 2009, 61:86-100.
12. Tarran R., Grubb B.R., Gatzy J.T., Davis C.W., Boucher R.C. The relative roles of passive surface forces and active ion transport in the modulation of airway surface liquid volume and composition. J. Gen. Physiol. 2001, 118:223-236.
13. Yeates D.B., Sturgess J.M., Kahn S.R., Levison H., Aspin N. Mucociliary transport in trachea of patients with cystic fibrosis. Arch. Dis. Child. 1976, 51:28-33.
14. Sanders N., Rudolph C., Braeckmans K., De Smedt S.C., Demeester J. Extracellular barriers in respiratory gene therapy. Adv. Drug Deliv. Rev. 2009, 61:115-127.
15. Sheils C.A., Kas J., Travassos W., Allen P.G., Janmey P.A., Wohl M.E., et al. Actin filaments mediate DNA fiber formation in chronic inflammatory airway disease. Am. J. Pathol. 1996, 148:919-927.
16. Patton J.S., Fishburn C.S., Weers J.G. The lungs as a portal of entry for systemic drug delivery. Proc. Am. Thorac. Soc. 2004, 1:338-344.
17. Brain J.D. Free cells in the lungs. Some aspects of their role, quantitation, and regulation. Arch. Intern Med. 1970, 126:477-487.
18. Geiser M. Update on macrophage clearance of inhaled micro- and nanoparticles. J. Aerosol. Med. Pulm. Drug Deliv. 2010, 23:207-217.
19. Ramsey J.M., Hibbitts A., Barlow J., Kelly C., Sivadas N., Cryan S.A. 'Smart' non-viral delivery systems for targeted delivery of RNAi to the lungs. Ther. Deliv. 2013, 4:59-76.
20. Merkel O.M., Kissel T. Nonviral pulmonary delivery of siRNA. Acc. Chem. Res. 2012, 45:961-970.
21. Davis P.B., Cooper M.J. Vectors for airway gene delivery. AAPS J. 2007, 9:E11-E17.
22. Ruiz F.E., Clancy J.P., Perricone M.A., Bebok Z., Hong J.S., Cheng S.H., et al. A clinical inflammatory syndrome attributable to aerosolized lipid-DNA administration in cystic fibrosis. Hum. Gene Ther. 2001, 12:751-761.
23. Brown M.D., Schatzlein A.G., Uchegbu I.F. Gene delivery with synthetic (non viral) carriers. Int. J. Pharm. 2001, 229:1-21.
24. Zou S.M., Erbacher P., Remy J.S., Behr J.P. Systemic linear polyethylenimine (L-PEI)-mediated gene delivery in the mouse. J. Gene Med. 2000, 2:128-134.
25. Griesenbach U., Pytel K.M., Alton E.W. Cystic fibrosis gene therapy in the UK and elsewhere. Hum. Gene Ther. 2015, 26:266-275.
26. Densmore C.L., Orson F.M., Xu B., Kinsey B.M., Waldrep J.C., Hua P., et al. Aerosol delivery of robust polyethyleneimine-DNA complexes for gene therapy and genetic immunization. Mol. Ther. 2000, 1:180-188.
27. Davies L.A., Seguela C., Varathalingam A., Cheng S.H., Hyde S.C., Gill D.R. Identification of transfected cell types following non-viral gene transfer to the murine lung. J. Gene Med. 2007, 9:184-196.
28. Liu G., Molas M., Grossmann G.A., Pasumarthy M., Perales J.C., Cooper M.J., et al. Biological properties of poly-L-lysine-DNA complexes generated by cooperative binding of the polycation. J. Biol. Chem. 2001, 276:34379-34387.
29. Jeong J.H., Park T.G. Poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers. J. Control Release 2002, 82:159-166.
30. Bikram M., Lee M., Chang C.W., Janat-Amsbury M.M., Kern S.E., Kim S.W. Long-circulating DNA-complexed biodegradable multiblock copolymers for gene delivery: degradation profiles and evidence of dysopsonization. J. Control Release 2005, 103:221-233.
31. Xiang J.J., Tang J.Q., Zhu S.G., Nie X.M., Lu H.B., Shen S.R., et al. IONP-PLL: a novel non-viral vector for efficient gene delivery. J. Gene Med. 2003, 5:803-817.
32. Zou Y., Tornos C., Qiu X., Lia M., Perez-Soler R. p53 aerosol formulation with low toxicity and high efficiency for early lung cancer treatment. Clin. Cancer Res. 2007, 13:4900-4908.
33. Koping-Hoggard M., Tubulekas I., Guan H., Edwards K., Nilsson M., Varum K.M., et al. Chitosan as a nonviral gene delivery system. Structure-property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo. Gene Ther. 2001, 8:1108-1121.
34. Tripathi S.K., Goyal R., Kumar P., Gupta K.C. Linear polyethylenimine-graft-chitosan copolymers as efficient DNA/siRNA delivery vectors in vitro and in vivo. Nanomedicine 2012, 8:337-345.
35. Germershaus O., Mao S., Sitterberg J., Bakowsky U., Kissel T. Gene delivery using chitosan, trimethyl chitosan or polyethylenglycol-graft-trimethyl chitosan block copolymers: establishment of structure-activity relationships in vitro. J. Control Release 2008, 125:145-154.
36. Issa M.M., Koping-Hoggard M., Tommeraas K., Varum K.M., Christensen B.E., Strand S.P., et al. Targeted gene delivery with trisaccharide-substituted chitosan oligomers in vitro and after lung administration in vivo. J. Control Release 2006, 115:103-112.
37. Malakooty Poor E., Baghaban Eslaminejad M., Gheibi N., Bagheri F., Atyabi F. Chitosan-pDNA nanoparticle characteristics determine the transfection efficacy of gene delivery to human mesenchymal stem cells. Artif. Cells Nanomed. Biotechnol. 2014, 42:376-384.
38. Okamoto H., Nishida S., Todo H., Sakakura Y., Iida K., Danjo K. Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process. J. Pharm. Sci. 2003, 92:371-380.
39. Mohri K., Okuda T., Mori A., Danjo K., Okamoto H. Optimized pulmonary gene transfection in mice by spray-freeze dried powder inhalation. J. Control Release 2010, 144:221-226.
40. Kukowska-Latallo J.F., Chen C., Eichman J., Bielinska A.U., Baker J.R. Enhancement of dendrimer-mediated transfection using synthetic lung surfactant exosurf neonatal in vitro. Biochem. Biophys. Res. Commun. 1999, 264:253-261.
41. Akhtar S., Benter I. Toxicogenomics of non-viral drug delivery systems for RNAi: potential impact on siRNA-mediated gene silencing activity and specificity. Adv. Drug Deliv. Rev. 2007, 59:164-182.
42. Omidi Y., Barar J. Induction of human alveolar epithelial cell growth factor receptors by dendrimeric nanostructures. Int. J. Toxicol. 2009, 28:113-122.
43. Li C., Liu H., Sun Y., Wang H., Guo F., Rao S., et al. PAMAM nanoparticles promote acute lung injury by inducing autophagic cell death through the Akt-TSC2-mTOR signaling pathway. J. Mol. Cell Biol. 2009, 1:37-45.
44. Weiss S.I., Sieverling N., Niclasen M., Maucksch C., Thunemann A.F., Mohwald H., et al. Uronic acids functionalized polyethyleneimine (PEI)-polyethyleneglycol (PEG)-graft-copolymers as novel synthetic gene carriers. Biomaterials 2006, 27:2302-2312.
45. Salvati A., Pitek A.S., Monopoli M.P., Prapainop K., Bombelli F.B., Hristov D.R., et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat. Nanotechnol. 2013, 8:137-143.
46. Elfinger M., Maucksch C., Rudolph C. Characterization of lactoferrin as a targeting ligand for nonviral gene delivery to airway epithelial cells. Biomaterials 2007, 28:3448-3455.
47. Ziady A.G., Kim J., Colla J., Davis P.B. Defining strategies to extend duration of gene expression from targeted compacted DNA vectors. Gene Ther. 2004, 11:1378-1390.
48. Elfinger M., Geiger J., Hasenpusch G., Uzgun S., Sieverling N., Aneja M.K., et al. Targeting of the beta(2)-adrenoceptor increases nonviral gene delivery to pulmonary epithelial cells in vitro and lungs in vivo. J. Control Release 2009, 135:234-241.
49. Ziady A.G., Kelley T.J., Milliken E., Ferkol T., Davis P.B. Functional evidence of CFTR gene transfer in nasal epithelium of cystic fibrosis mice in vivo following luminal application of DNA complexes targeted to the serpin-enzyme complex receptor. Mol. Ther. 2002, 5:413-419.
50. Luo Y., Zhai X., Ma C., Sun P., Fu Z., Liu W., et al. An inhalable beta(2)-adrenoceptor ligand-directed guanidinylated chitosan carrier for targeted delivery of siRNA to lung. J. Control Release 2012, 162:28-36.
51. Elfinger M., Pfeifer C., Uezguen S., Golas M.M., Sander B., Maucksch C., et al. Self-assembly of ternary insulin-polyethylenimine (PEI)-DNA nanoparticles for enhanced gene delivery and expression in alveolar epithelial cells. Biomacromolecules 2009, 10:2912-2920.
52. Geiger J., Aneja M.K., Hasenpusch G., Yuksekdag G., Kummerlowe G., Luy B., et al. Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues. Biomaterials 2010, 31:2903-2911.
53. Hasenpusch G., Geiger J., Wagner K., Mykhaylyk O., Wiekhorst F., Trahms L., et al. Magnetized aerosols comprising superparamagnetic iron oxide nanoparticles improve targeted drug and gene delivery to the lung. Pharm. Res. 2012, 29:1308-1318.
54. Dames P., Laner A., Maucksch C., Aneja M.K., Rudolph C. Targeting of the glucocorticoid hormone receptor with plasmid DNA comprising glucocorticoid response elements improves nonviral gene transfer efficiency in the lungs of mice. J. Gene Med. 2007, 9:820-829.
55. Parker A.L., Newman C., Briggs S., Seymour L., Sheridan P.J. Nonviral gene delivery: techniques and implications for molecular medicine. Expert Rev. Mol. Med. 2003, 5:1-15.
56. Oudrhiri N., Vigneron J.P., Peuchmaur M., Leclerc T., Lehn J.M., Lehn P. Gene transfer by guanidinium-cholesterol cationic lipids into airway epithelial cells in vitro and in vivo. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:1651-1656.
57. Li S., Huang L. In vivo gene transfer via intravenous administration of cationic lipid-protamine-DNA (LPD) complexes. Gene Ther. 1997, 4:891-900.
58. Noone P.G., Hohneker K.W., Zhou Z., Johnson L.G., Foy C., Gipson C., et al. Safety and biological efficacy of a lipid-CFTR complex for gene transfer in the nasal epithelium of adult patients with cystic fibrosis. Mol. Ther. 2000, 1:105-114.
59. Urtti A., Polansky J., Lui G.M., Szoka F.C. Gene delivery and expression in human retinal pigment epithelial cells: effects of synthetic carriers, serum, extracellular matrix and viral promoters. J. Drug Target 2000, 7:413-421.
60. Konopka K., Fallah B., Monzon-Duller J., Overlid N., Duzgunes N. Serum-resistant gene transfer to oral cancer cells by Metafectene and GeneJammer: application to HSV-tk/ganciclovir-mediated cytotoxicity. Cell Mol. Biol. Lett. 2005, 10:455-470.
61. Stavridis J.C., Deliconstantinos G., Psallidopoulos M.C., Armenakas N.A., Hadjiminas D.J., Hadjiminas J. Construction of transferrin-coated liposomes for in vivo transport of exogenous DNA to bone marrow erythroblasts in rabbits. Exp. Cell Res. 1986, 164:568-572.
62. Willis M., Forssen E. Ligand-targeted liposomes. Adv. Drug Deliv. Rev. 1998, 29:249-271.
63. Allon N., Saxena A., Chambers C., Doctor B.P. A new liposome-based gene delivery system targeting lung epithelial cells using endothelin antagonist. J. Control Release 2012, 160:217-224.
64. Tagalakis A.D., McAnulty R.J., Devaney J., Bottoms S.E., Wong J.B., Elbs M., et al. A receptor-targeted nanocomplex vector system optimized for respiratory gene transfer. Mol. Ther. 2008, 16:907-915.
65. Berger M. Inflammatory mediators in cystic fibrosis lung disease. Allergy Asthma Proc. 2002, 23:19-25.
66. Baatz J.E., Zou Y., Korfhagen T.R. Inhibitory effects of tumor necrosis factor-alpha on cationic lipid-mediated gene delivery to airway cells in vitro. Biochim. Biophys. Acta 2001, 1535:100-109.
67. Bastonero S., Gargouri M., Ortiou S., Gueant J.L., Merten M.D. Inhibition by TNF-alpha and IL-4 of cationic lipid mediated gene transfer in cystic fibrosis tracheal gland cells. J. Gene Med. 2005, 7:1439-1449.
68. Pavic I., Polic B., Crnkovic I., Lucin P., Jonjic S., Koszinowski U.H. Participation of endogenous tumour necrosis factor alpha in host resistance to cytomegalovirus infection. J. Gen. Virol. 1993, 74(Pt 10):2215-2223.
69. Alfaro-Moreno E., Nawrot T.S., Vanaudenaerde B.M., Hoylaerts M.F., Vanoirbeek J.A., Nemery B., et al. Co-cultures of multiple cell types mimic pulmonary cell communication in response to urban PM10. Eur. Respir. J. 2008, 32:1184-1194.
70. Lehmann A.D., Daum N., Bur M., Lehr C.M., Gehr P., Rothen-Rutishauser B.M. An in vitro triple cell co-culture model with primary cells mimicking the human alveolar epithelial barrier. Eur. J. Pharm. Biopharm. 2011, 77:398-406.
71. Hermanns M.I., Kasper J., Dubruel P., Pohl C., Uboldi C., Vermeersch V., et al. An impaired alveolar-capillary barrier in vitro: effect of proinflammatory cytokines and consequences on nanocarrier interaction. J. R. Soc. Interface 2010, 7(Suppl. 1):S41-S54.
72. Rosenecker J., Naundorf S., Gersting S.W., Hauck R.W., Gessner A., Nicklaus P., et al. Interaction of bronchoalveolar lavage fluid with polyplexes and lipoplexes: analysing the role of proteins and glycoproteins. J. Gene Med. 2003, 5:49-60.
73. Lamblin G., Aubert J.P., Perini J.M., Klein A., Porchet N., Degand P., et al. Human respiratory mucins. Eur. Respir. J. 1992, 5:247-256.
74. Carlstedt I., Sheehan J.K., Corfield A.P., Gallagher J.T. Mucous glycoproteins: a gel of a problem. Essays Biochem. 1985, 20:40-76.
75. Bansil R., Stanley E., LaMont J.T. Mucin biophysics. Annu. Rev. Physiol. 1995, 57:635-657.
76. Henke M.O., Renner A., Huber R.M., Seeds M.C., Rubin B.K. MUC5AC and MUC5B mucins are decreased in cystic fibrosis airway secretions. Am. J. Respir. Cell Mol. Biol. 2004, 31:86-91.
77. Sanders N.N., Van Rompaey E., De Smedt S.C., Demeester J. Structural alterations of gene complexes by cystic fibrosis sputum. Am. J. Respir. Crit. Care Med. 2001, 164:486-493.
78. Jinnai M., Niimi A., Ueda T., Matsuoka H., Takemura M., Yamaguchi M., et al. Induced sputum concentrations of mucin in patients with asthma and chronic cough. Chest 2010, 137:1122-1129.
79. Rogers D.F., Barnes P.J. Treatment of airway mucus hypersecretion. Ann. Med. 2006, 38:116-125.
80. Kater A., Henke M.O., Rubin B.K. The role of DNA and actin polymers on the polymer structure and rheology of cystic fibrosis sputum and depolymerization by gelsolin or thymosin beta 4. Ann. N. Y. Acad. Sci. 2007, 1112:140-153.
81. Olmsted S.S., Padgett J.L., Yudin A.I., Whaley K.J., Moench T.R., Cone R.A. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys. J. 2001, 81:1930-1937.
82. Ruponen M., Yla-Herttuala S., Urtti A. Interactions of polymeric and liposomal gene delivery systems with extracellular glycosaminoglycans: physicochemical and transfection studies. Biochim. Biophys. Acta 1999, 1415:331-341.
83. Carrabino S., Di Gioia S., Copreni E., Conese M. Serum albumin enhances polyethylenimine-mediated gene delivery to human respiratory epithelial cells. J. Gene Med. 2005, 7:1555-1564.
84. Stern M., Caplen N.J., Browning J.E., Griesenbach U., Sorgi F., Huang L., et al. The effect of mucolytic agents on gene transfer across a CF sputum barrier in vitro. Gene Ther. 1998, 5:91-98.
85. Kleemann E., Neu M., Jekel N., Fink L., Schmehl T., Gessler T., et al. Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI. J. Control Release 2005, 109:299-316.
86. Mosqueira V.C., Legrand P., Morgat J.L., Vert M., Mysiakine E., Gref R., et al. Biodistribution of long-circulating PEG-grafted nanocapsules in mice: effects of PEG chain length and density. Pharm. Res. 2001, 18:1411-1419.
87. Lee M., Kim S.W. Polyethylene glycol-conjugated copolymers for plasmid DNA delivery. Pharm. Res. 2005, 22:1-10.
88. Thompson B., Mignet N., Hofland H., Lamons D., Seguin J., Nicolazzi C., et al. Neutral postgrafted colloidal particles for gene delivery. Bioconjug. Chem. 2005, 16:608-614.
89. Meyer M., Wagner E. pH-responsive shielding of non-viral gene vectors. Expert Opin. Drug Deliv. 2006, 3:563-571.
90. Sanders N.N., De Smedt S.C., Cheng S.H., Demeester J. Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus. Gene Ther. 2002, 9:363-371.
91. Beyerle A., Merkel O., Stoeger T., Kissel T. PEGylation affects cytotoxicity and cell-compatibility of poly(ethylene imine) for lung application: structure-function relationships. Toxicol. Appl. Pharmacol. 2010, 242:146-154.
92. Kleemann E., Jekel N., Dailey L.A., Roesler S., Fink L., Weissmann N., et al. Enhanced gene expression and reduced toxicity in mice using polyplexes of low-molecular-weight poly(ethylene imine) for pulmonary gene delivery. J. Drug Target 2009, 17:638-651.
93. Rudolph C., Schillinger U., Plank C., Gessner A., Nicklaus P., Muller R., et al. Nonviral gene delivery to the lung with copolymer-protected and transferrin-modified polyethylenimine. Biochim. Biophys. Acta 2002, 1573:75-83.
94. Sanders N.N., De Smedt S.C., Demeester J. Mobility and stability of gene complexes in biogels. J. Control Release 2003, 87:117-129.
95. Nguyen J., Xie X., Neu M., Dumitrascu R., Reul R., Sitterberg J., et al. Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs. J. Gene Med. 2008, 10:1236-1246.
96. Hibbitts A., Lieggi N., McCabe O., Thomas W., Barlow J., O'Brien F., et al. Screening of siRNA nanoparticles for delivery to airway epithelial cells using high-content analysis. Ther. Deliv. 2011, 2:987-999.
97. Uchida S., Itaka K., Chen Q., Osada K., Ishii T., Shibata M.A., et al. PEGylated polyplex with optimized PEG shielding enhances gene introduction in lungs by minimizing inflammatory responses. Mol. Ther. 2012, 20:1196-1203.
98. Wang Y.Y., Lai S.K., Suk J.S., Pace A., Cone R., Hanes J. Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that "slip" through the human mucus barrier. Angew. Chem. Int. Ed. Engl. 2008, 47:9726-9729.
99. Suk J.S., Lai S.K., Wang Y.Y., Ensign L.M., Zeitlin P.L., Boyle M.P., et al. The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles. Biomaterials 2009, 30:2591-2597.
100. Tang B.C., Dawson M., Lai S.K., Wang Y.Y., Suk J.S., Yang M., et al. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:19268-19273.
101. Petersen H., Fechner P.M., Martin A.L., Kunath K., Stolnik S., Roberts C.J., et al. Polyethylenimine-graft-poly(ethylene glycol) copolymers: influence of copolymer block structure on DNA complexation and biological activities as gene delivery system. Bioconjug. Chem. 2002, 13:845-854.
102. Kim A.J., Boylan N.J., Suk J.S., Hwangbo M., Yu T., Schuster B.S., et al. Use of single-site-functionalized PEG dendrons to prepare gene vectors that penetrate human mucus barriers. Angew. Chem. Int. Ed. Engl. 2013, 52:3985-3988.
103. Suk J.S., Kim A.J., Trehan K., Schneider C.S., Cebotaru L., Woodward O.M., et al. Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier. J. Control Release 2014, 178C:8-17.
104. Shah P.L., Scott S.F., Knight R.A., Hodson M.E. The effects of recombinant human DNase on neutrophil elastase activity and interleukin-8 levels in the sputum of patients with cystic fibrosis. Eur. Respir. J. 1996, 9:531-534.
105. Sanders N.N., De Smedt S.C., Van Rompaey E., Simoens P., De Baets F., Demeester J. Cystic fibrosis sputum: a barrier to the transport of nanospheres. Am. J. Respir. Crit. Care Med. 2000, 162:1905-1911.
106. Antonicelli F., Brown D., Parmentier M., Drost E.M., Hirani N., Rahman I., et al. Regulation of LPS-mediated inflammation in vivo and in vitro by the thiol antioxidant Nacystelyn. Am. J. Physiol. Lung Cell Mol. Physiol. 2004, 286:L1319-L1327.
107. Vosters O., Neve J., De Wit D., Willems F., Goldman M., Verhasselt V. Dendritic cells exposed to nacystelyn are refractory to maturation and promote the emergence of alloreactive regulatory t cells. Transplantation 2003, 75:383-389.
108. Kitson C., Angel B., Judd D., Rothery S., Severs N.J., Dewar A., et al. The extra- and intracellular barriers to lipid and adenovirus-mediated pulmonary gene transfer in native sheep airway epithelium. Gene Ther. 1999, 6:534-546.
109. Ferrari S., Kitson C., Farley R., Steel R., Marriott C., Parkins D.A., et al. Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium. Gene Ther. 2001, 8:1380-1386.
110. Sanders N.N., Van Rompaey E., De Smedt S.C., Demeester J. On the transport of lipoplexes through cystic fibrosis sputum. Pharm. Res. 2002, 19:451-456.
111. Dawson M., Wirtz D., Hanes J. Enhanced viscoelasticity of human cystic fibrotic sputum correlates with increasing microheterogeneity in particle transport. J. Biol. Chem. 2003, 278:50393-50401.
112. Broughton-Head V.J., Smith J.R., Shur J., Shute J.K. Actin limits enhancement of nanoparticle diffusion through cystic fibrosis sputum by mucolytics. Pulm. Pharmacol. Ther. 2007, 20:708-717.
113. Hida K., Lai S.K., Suk J.S., Won S.Y., Boyle M.P., Hanes J. Common gene therapy viral vectors do not efficiently penetrate sputum from cystic fibrosis patients. PLoS One 2011, 6:e19919.
114. Suk J.S., Boylan N.J., Trehan K., Tang B.C., Schneider C.S., Lin J.M., et al. N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles. Mol. Ther. 2011, 19:1981-1989.
115. Laube B.L. The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update. Transl. Respir. Med. 2014, 2:3.
116. Maes T., Tournoy K.G., Joos G.F. Gene therapy for allergic airway diseases. Curr. Allergy Asthma Rep. 2011, 11:163-172.
117. Kumar M., Kong X., Behera A.K., Hellermann G.R., Lockey R.F., Mohapatra S.S. Chitosan IFN-gamma-pDNA nanoparticle (CIN) therapy for allergic asthma. Genet. Vaccines Ther. 2003, 1:3.
118. Kong X., Hellermann G.R., Zhang W., Jena P., Kumar M., Behera A., et al. Chitosan interferon-gamma nanogene therapy for lung disease: modulation of T-cell and dendritic cell immune responses. Allergy Asthma Clin. Immunol. 2008, 4:95-105.
119. Konstan M.W., Davis P.B., Wagener J.S., Hilliard K.A., Stern R.C., Milgram L.J., et al. Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution. Hum. Gene Ther. 2004, 15:1255-1269.
120. Yara S., Kawakami K., Kudeken N., Tohyama M., Teruya K., Chinen T., et al. FTS reduces bleomycin-induced cytokine and chemokine production and inhibits pulmonary fibrosis in mice. Clin. Exp. Immunol. 2001, 124:77-85.
121. Henriques-Coelho T., Oliveira S.M., Moura R.S., Roncon-Albuquerque R., Neves A.L., Santos M., et al. Thymulin inhibits monocrotaline-induced pulmonary hypertension modulating interleukin-6 expression and suppressing p38 pathway. Endocrinology 2008, 149:4367-4373.
122. da Silva A.L., Martini S.V., Abreu S.C., Samary Cdos S., Diaz B.L., Fernezlian S., et al. DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma. J. Control Release 2014, 180:125-133.
123. Hong S.H., Park S.J., Lee S., Cho C.S., Cho M.H. Aerosol gene delivery using viral vectors and cationic carriers for in vivo lung cancer therapy. Expert Opin. Drug Deliv. 2015, 12:977-991.
124. Zarogoulidis P., Darwiche K., Hohenforst-Schmidt W., Huang H., Li Q., Freitag L., et al. Inhaled gene therapy in lung cancer: proof-of-concept for nano-oncology and nanobiotechnology in the management of lung cancer. Future Oncol. 2013, 9:1171-1194.
125. Asai T., Oku N. Systemic delivery of small RNA using lipid nanoparticles. Biol. Pharm. Bull. 2014, 37:201-205.
126. Watts J.K., Corey D.R. Silencing disease genes in the laboratory and the clinic. J. Pathol. 2012, 226:365-379.
127. Chan J.H., Lim S., Wong W.S. Antisense oligonucleotides: from design to therapeutic application. Clin. Exp. Pharmacol. Physiol. 2006, 33:533-540.
128. Movassaghian S., Moghimi H.R., Shirazi F.H., Koshkaryev A., Trivedi M.S., Torchilin V.P. Efficient down-regulation of PKC-alpha gene expression in A549 lung cancer cells mediated by antisense oligodeoxynucleotides in dendrosomes. Int. J. Pharm. 2013, 441:82-91.
129. Fujita Y., Takeshita F., Kuwano K., Ochiya T. RNAi therapeutic platforms for lung diseases. Pharmaceuticals (Basel) 2013, 6:223-250.
130. Kim Y.D., Park T.E., Singh B., Maharjan S., Choi Y.J., Choung P.H., et al. Nanoparticle-mediated delivery of siRNA for effective lung cancer therapy. Nanomedicine (Lond) 2015, 10:1165-1188.
131. Lam J.K., Liang W., Chan H.K. Pulmonary delivery of therapeutic siRNA. Adv. Drug Deliv. Rev. 2012, 64:1-15.
132. Shim G., Choi H.W., Lee S., Choi J., Yu Y.H., Park D.E., et al. Enhanced intrapulmonary delivery of anticancer siRNA for lung cancer therapy using cationic ethylphosphocholine-based nanolipoplexes. Mol. Ther. 2013, 21:816-824.
133. Song L., Coppola D., Livingston S., Cress D., Haura E.B. Mcl-1 regulates survival and sensitivity to diverse apoptotic stimuli in human non-small cell lung cancer cells. Cancer Biol. Ther. 2005, 4:267-276.
134. Luo L., Zhang T., Liu H., Lv T., Yuan D., Yao Y., et al. MiR-101 and Mcl-1 in non-small-cell lung cancer: expression profile and clinical significance. Med. Oncol. 2012, 29:1681-1686.
135. Fehring V., Schaeper U., Ahrens K., Santel A., Keil O., Eisermann M., et al. Delivery of therapeutic siRNA to the lung endothelium via novel Lipoplex formulation DACC. Mol. Ther. 2014, 22:811-820.
136. DeLisser H., Liu Y., Desprez P.Y., Thor A., Briasouli P., Handumrongkul C., et al. Vascular endothelial platelet endothelial cell adhesion molecule 1 (PECAM-1) regulates advanced metastatic progression. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:18616-18621.
137. McCarroll J.A., Dwarte T., Baigude H., Dang J., Yang L., Erlich R.B., et al. Therapeutic targeting of polo-like kinase 1 using RNA-interfering nanoparticles (iNOPs) for the treatment of non-small cell lung cancer. Oncotarget 2015, 6:12020-12034.
138. Yu H., Zou Y., Jiang L., Yin Q., He X., Chen L., et al. Induction of apoptosis in non-small cell lung cancer by downregulation of MDM2 using pH-responsive PMPC-b-PDPA/siRNA complex nanoparticles. Biomaterials 2013, 34:2738-2747.
139. Zhang Y., Schwerbrock N.M., Rogers A.B., Kim W.Y., Huang L. Codelivery of VEGF siRNA and gemcitabine monophosphate in a single nanoparticle formulation for effective treatment of NSCLC. Mol. Ther. 2013, 21:1559-1569.
140. Andries O., De Filette M., De Smedt S.C., Demeester J., Van Poucke M., Peelman L., et al. Innate immune response and programmed cell death following carrier-mediated delivery of unmodified mRNA to respiratory cells. J. Control Release 2013, 167:157-166.
141. Yamamoto A., Kormann M., Rosenecker J., Rudolph C. Current prospects for mRNA gene delivery. Eur. J. Pharm. Biopharm. 2009, 71:484-489.
142. Mattes J., Yang M., Foster P.S. Regulation of microRNA by antagomirs: a new class of pharmacological antagonists for the specific regulation of gene function?. Am. J. Respir. Cell Mol. Biol. 2007, 36:8-12.
143. Fortunato O., Boeri M., Verri C., Moro M., Sozzi G. Therapeutic use of microRNAs in lung cancer. Biomed. Res. Int. 2014, 2014:756975.
144. Shi S., Han L., Gong T., Zhang Z., Sun X. Systemic delivery of microRNA-34a for cancer stem cell therapy. Angew. Chem. Int. Ed. Engl. 2013, 52:3901-3905.
145. Wu Y., Crawford M., Mao Y., Lee R.J., Davis I.C., Elton T.S., et al. Therapeutic delivery of microRNA-29b by cationic lipoplexes for lung cancer. Mol. Ther. Nucleic Acids 2013, 2:e84.
146. Cortez M.A., Valdecanas D., Zhang X., Zhan Y., Bhardwaj V., Calin G.A., et al. Therapeutic delivery of miR-200c enhances radiosensitivity in lung cancer. Mol. Ther. 2014, 22:1494-1503.
147. Shi S., Han L., Deng L., Zhang Y., Shen H., Gong T., et al. Dual drugs (microRNA-34a and paclitaxel)-loaded functional solid lipid nanoparticles for synergistic cancer cell suppression. J. Control Release 2014, 194:228-237.
148. Tzortzaki E.G., Papi A., Neofytou E., Soulitzis N., Siafakas N.M. Immune and genetic mechanisms in COPD: possible targets for therapeutic interventions. Curr. Drug Targets 2013, 14:141-148.
149. Mueller C., Flotte T.R. Gene-based therapy for alpha-1 antitrypsin deficiency. COPD 2013, 10(Suppl. 1):44-49.
150. Brigham K.L., Lane K.B., Meyrick B., Stecenko A.A., Strack S., Cannon D.R., et al. Transfection of nasal mucosa with a normal alpha1-antitrypsin gene in alpha1-antitrypsin-deficient subjects: comparison with protein therapy. Hum. Gene Ther. 2000, 11:1023-1032.
151. Wewers M.D., Crystal R.G. Alpha-1 antitrypsin augmentation therapy. COPD 2013, 10(Suppl. 1):64-67.
152. d'Angelo I., Conte C., La Rotonda M.I., Miro A., Quaglia F., Ungaro F. Improving the efficacy of inhaled drugs in cystic fibrosis: challenges and emerging drug delivery strategies. Adv. Drug Deliv. Rev. 2014, 75:92-111.
153. McLachlan G., Davidson H., Holder E., Davies L.A., Pringle I.A., Sumner-Jones S.G., et al. Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung. Gene Ther. 2011, 18:996-1005.
154. Alton E.W., Stern M., Farley R., Jaffe A., Chadwick S.L., Phillips J., et al. Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet 1999, 353:947-954.
155. Hyde S.C., Pringle I.A., Abdullah S., Lawton A.E., Davies L.A., Varathalingam A., et al. CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression. Nat. Biotechnol. 2008, 26:549-551.
156. Davies L.A., Nunez-Alonso G.A., McLachlan G., Hyde S.C., Gill D.R. Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy. Hum. Gene Ther. Clin. Dev. 2014, 25:97-107.
157. Horsley A.R., Davies J.C., Gray R.D., Macleod K.A., Donovan J., Aziz Z.A., et al. Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation. Thorax 2013, 68:532-539.
158. Zarogouldis P., Karamanos N.K., Porpodis K., Domvri K., Huang H., Hohenforst-Schimdt W., et al. Vectors for inhaled gene therapy in lung cancer. Application for nano oncology and safety of bio nanotechnology. Int. J. Mol. Sci. 2012, 13:10828-10862.
159. Bahadori M., Mohammadi F. Nanomedicine for respiratory diseases. Tanaffos 2012, 11:18-22.
160. Ramesh R. Nanoparticle-mediated gene delivery to the lung. Methods Mol. Biol. 2008, 433:301-331.
161. Lu C., Stewart D.J., Lee J.J., Ji L., Ramesh R., Jayachandran G., et al. Phase I clinical trial of systemically administered TUSC2(FUS1)-nanoparticles mediating functional gene transfer in humans. PLoS One 2012, 7:e34833.
162. Wistuba I.I., Behrens C., Milchgrub S., Bryant D., Hung J., Minna J.D., et al. Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. Oncogene 1999, 18:643-650.
163. Templeton N.S., Senzer N. Optimization of non-viral gene therapeutics using bilamellar invaginated vesicles. J. Genet. Syndr. Gene Ther. 2011, S5:002.
164. Nafee N., Husari A., Maurer C.K., Lu C., de Rossi C., Steinbach A., et al. Antibiotic-free nanotherapeutics: ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors. J. Control Release 2014, 192:131-140.
165. Johnson L.G., Olsen J.C., Sarkadi B., Moore K.L., Swanstrom R., Boucher R.C. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat. Genet. 1992, 2:21-25.
166. Potash A.E., Wallen T.J., Karp P.H., Ernst S., Moninger T.O., Gansemer N.D., et al. Adenoviral gene transfer corrects the ion transport defect in the sinus epithelia of a porcine CF model. Mol. Ther. 2013, 21:947-953.
167. Cipolla D., Shekunov B., Blanchard J., Hickey A. Lipid-based carriers for pulmonary products: preclinical development and case studies in humans. Adv. Drug Deliv. Rev. 2014, 75:53-80.
168. Lee W.H., Loo C.Y., Traini D., Young P.M. Nano- and micro-based inhaled drug delivery systems for targeting alveolar macrophages. Expert Opin. Drug Deliv. 2015, 1-18.
169. de Souza Carvalho C., Daum N., Lehr C.M. Carrier interactions with the biological barriers of the lung: advanced in vitro models and challenges for pulmonary drug delivery. Adv. Drug Deliv. Rev. 2014, 75:129-140.
170. NCT01315678 and NCT01315236. http://clinicaltrials.gov.