REFERENCES

1. Murray, J. F. The structure and function of the lung. Int. J. Tuberc. Lung. Dis. 2010, 14, 391-6.

2. Weibel, E. R. Lung morphometry: the link between structure and function. Cell. Tissue. Res. 2017, 367, 413-26.

3. Pettigrew, M. M.; Tanner, W.; Harris, A. D. The lung microbiome and pneumonia. J. Infect. Dis. 2021, 223, S241-5.

4. Mokrá, D. Acute lung injury - from pathophysiology to treatment. Physiol. Res. 2020, 69, S353-66.

5. Alfahad, A. J.; Alzaydi, M. M.; Aldossary, A. M.; et al. Current views in chronic obstructive pulmonary disease pathogenesis and management. Saudi. Pharm. J. 2021, 29, 1361-73.

6. Rafeeq, M. M.; Murad, H. A. S. Cystic fibrosis: current therapeutic targets and future approaches. J. Transl. Med. 2017, 15, 84.

7. Nasim, F.; Sabath, B. F.; Eapen, G. A. Lung cancer. Med. Clin. North. Am. 2019, 103, 463-73.

8. 2019 Chronic Respiratory Diseases Collaborators. Global burden of chronic respiratory diseases and risk factors, 1990-2019: an update from the Global Burden of Disease Study 2019. EClinicalMedicine 2023, 59, 101936.

9. Sahu, I.; Haque, A. K. M. A.; Weidensee, B.; Weinmann, P.; Kormann, M. S. D. Recent developments in mRNA-based protein supplementation therapy to target lung diseases. Mol. Ther. 2019, 27, 803-23.

10. Maruggi, G.; Zhang, C.; Li, J.; Ulmer, J. B.; Yu, D. mRNA as a Transformative technology for vaccine development to control infectious diseases. Mol. Ther. 2019, 27, 757-72.

11. Ishii, K. J.; Akira, S. TLR ignores methylated RNA? Immunity 2005, 23, 111-3.

12. Karikó, K.; Ni, H.; Capodici, J.; Lamphier, M.; Weissman, D. mRNA is an endogenous ligand for Toll-like receptor 3. J. Biol. Chem. 2004, 279, 12542-50.

13. Cullis, P. R.; Hope, M. J. Lipid nanoparticle systems for enabling gene therapies. Mol. Ther. 2017, 25, 1467-75.

14. Chatterjee, S.; Kon, E.; Sharma, P.; Peer, D. Endosomal escape: a bottleneck for LNP-mediated therapeutics. Proc. Natl. Acad. Sci. U. S. A. 2024, 121, e2307800120.

15. John, R.; Monpara, J.; Swaminathan, S.; Kalhapure, R. Chemistry and art of developing lipid nanoparticles for biologics delivery: focus on development and scale-up. Pharmaceutics 2024, 16, 131.

16. Gilbert, J.; Sebastiani, F.; Arteta, M. Y.; et al. Evolution of the structure of lipid nanoparticles for nucleic acid delivery: From in situ studies of formulation to colloidal stability. J. Colloid. Interface. Sci. 2024, 660, 66-76.

17. Mehta, M.; Bui, T. A.; Yang, X.; Aksoy, Y.; Goldys, E. M.; Deng, W. Lipid-Based nanoparticles for drug/gene delivery: an overview of the production techniques and difficulties encountered in their industrial development. ACS. Mater. Au. 2023, 3, 600-19.

18. Cheng, X.; Lee, R. J. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. Adv. Drug. Deliv. Rev. 2016, 99, 129-37.

19. Schober, G. B.; Story, S.; Arya, D. P. A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient. Sci. Rep. 2024, 14, 2403.

20. Wu, S.; Lin, L.; Shi, L.; Liu, S. An overview of lipid constituents in lipid nanoparticle mRNA delivery systems. Wiley. Interdiscip. Rev. Nanomed. Nanobiotechnol. 2024, 16, e1978.

21. Zhang, Y.; Sun, C.; Wang, C.; Jankovic, K. E.; Dong, Y. Lipids and lipid derivatives for RNA delivery. Chem. Rev. 2021, 121, 12181-277.

22. Miao, L.; Zhang, Y.; Huang, L. mRNA vaccine for cancer immunotherapy. Mol. Cancer. 2021, 20, 41.

23. Jung, O.; Jung, H. Y.; Thuy, L. T.; et al. Modulating lipid nanoparticles with histidinamide-conjugated cholesterol for improved intracellular delivery of mRNA. Adv. Healthc. Mater. 2024, 13, e2303857.

24. Hajj, K. A.; Ball, R. L.; Deluty, S. B.; et al. Branched-tail lipid nanoparticles potently deliver mRNA in vivo due to enhanced ionization at endosomal pH. Small 2019, 15, e1805097.

25. Eygeris, Y.; Gupta, M.; Kim, J.; Sahay, G. Chemistry of lipid nanoparticles for RNA Delivery. Acc. Chem. Res. 2022, 55, 2-12.

26. Suk, J. S.; Xu, Q.; Kim, N.; Hanes, J.; Ensign, L. M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug. Deliv. Rev. 2016, 99, 28-51.

27. Schoenmaker, L.; Witzigmann, D.; Kulkarni, J. A.; et al. mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability. Int. J. Pharm. 2021, 601, 120586.

28. Huang, X.; Ma, Y.; Ma, G.; Xia, Y. Unlocking the therapeutic applicability of LNP-mRNA: chemistry, formulation, and clinical strategies. Research. (Wash. D. C). 2024, 7, 0370.

29. Ibrahim, M.; Ramadan, E.; Elsadek, N. E.; et al. Polyethylene glycol (PEG): the nature, immunogenicity, and role in the hypersensitivity of PEGylated products. J. Control. Release. 2022, 351, 215-30.

30. Tenchov, R.; Sasso, J. M.; Zhou, Q. A. PEGylated lipid nanoparticle formulations: immunological safety and efficiency perspective. Bioconjug. Chem. 2023, 34, 941-60.

31. Zong, Y.; Lin, Y.; Wei, T.; Cheng, Q. Lipid nanoparticle (LNP) enables mRNA DElivery for cancer therapy. Adv. Mater. 2023, 35, e2303261.

32. Maeki, M.; Uno, S.; Niwa, A.; Okada, Y.; Tokeshi, M. Microfluidic technologies and devices for lipid nanoparticle-based RNA delivery. J. Control. Release. 2022, 344, 80-96.

33. Geng, C.; Zhou, K.; Yan, Y.; et al. A preparation method for mRNA-LNPs with improved properties. J. Control. Release. 2023, 364, 632-43.

34. Sackmann, E. K.; Fulton, A. L.; Beebe, D. J. The present and future role of microfluidics in biomedical research. Nature 2014, 507, 181-9.

35. Damiati, S.; Kompella, U. B.; Damiati, S. A.; Kodzius, R. Microfluidic devices for drug delivery systems and drug screening. Genes. (Basel). 2018, 9, 103.

36. Shepherd, S. J.; Warzecha, C. C.; Yadavali, S.; et al. Scalable mRNA and siRNA lipid nanoparticle production using a parallelized microfluidic device. Nano. Lett. 2021, 21, 5671-80.

37. Subraveti, S. N.; Wilson, B. K.; Bizmark, N.; Liu, J.; Prud'homme, R. K. Synthesizing Lipid nanoparticles by turbulent flow in confined impinging jet mixers. J. Vis. Exp. 2024. DOI: 10.3791/67047.

38. O'Brien, L. M. N.; Costa, A. P.; Cebrero, Y. M.; et al. Process robustness in lipid nanoparticle production: a comparison of microfluidic and turbulent jet mixing. Mol. Pharm. 2023, 20, 4285-96.

39. Pratsinis, A.; Fan, Y.; Portmann, M.; et al. Impact of non-ionizable lipids and phase mixing methods on structural properties of lipid nanoparticle formulations. Int. J. Pharm. 2023, 637, 122874.

40. Cui, L.; Pereira, S.; Sonzini, S.; et al. Development of a high-throughput platform for screening lipid nanoparticles for mRNA delivery. Nanoscale 2022, 14, 1480-91.

41. Bai, C.; Wang, C.; Lu, Y. Novel vectors and administrations for mRNA delivery. Small 2023, 19, e2303713.

42. Wang, J.; Ding, Y.; Chong, K.; et al. Recent advances in lipid nanoparticles and their safety concerns for mRNA delivery. Vaccines. (Basel). 2024, 12, 1148.

43. Wang, C.; Zhang, Y.; Dong, Y. Lipid nanoparticle-mRNA formulations for therapeutic applications. Acc. Chem. Res. 2021, 54, 4283-93.

44. Xiao, Y.; Tang, Z.; Huang, X.; et al. Emerging mRNA technologies: delivery strategies and biomedical applications. Chem. Soc. Rev. 2022, 51, 3828-45.

45. El-Mayta, R.; Padilla, M. S.; Billingsley, M. M.; Han, X.; Mitchell, M. J. Testing the in vitro and in vivo efficiency of mRNA-lipid nanoparticles formulated by microfluidic mixing. J. Vis. Exp. 2023. DOI: 10.3791/64810.

46. Liu, Y.; Huang, Y.; He, G.; Guo, C.; Dong, J.; Wu, L. Development of mRNA lipid nanoparticles: targeting and therapeutic aspects. Int. J. Mol. Sci. 2024, 25, 10166.

47. Hajiaghapour, A. M.; Dayani, F.; Saedi, S. F.; et al. Lipid nanoparticles as promising carriers for mRNA vaccines for viral lung infections. Pharmaceutics 2023, 15, 1127.

48. Cullis, P. R.; Felgner, P. L. The 60-year evolution of lipid nanoparticles for nucleic acid delivery. Nat. Rev. Drug. Discov. 2024, 23, 709-22.

49. Igyártó, B. Z.; Qin, Z. The mRNA-LNP vaccines - the good, the bad and the ugly? Front. Immunol. 2024, 15, 1336906.

50. Liu, J.; Cabral, H.; Mi, P. Nanocarriers address intracellular barriers for efficient drug delivery, overcoming drug resistance, subcellular targeting and controlled release. Adv. Drug. Deliv. Rev. 2024, 207, 115239.

51. Jiao, X.; He, X.; Qin, S.; et al. Insights into the formulation of lipid nanoparticles for the optimization of mRNA therapeutics. Wiley. Interdiscip. Rev. Nanomed. Nanobiotechnol. 2024, 16, e1992.

52. Weng, Y.; Xiao, H.; Zhang, J.; Liang, X. J.; Huang, Y. RNAi therapeutic and its innovative biotechnological evolution. Biotechnol. Adv. 2019, 37, 801-25.

53. Barbier, A. J.; Jiang, A. Y.; Zhang, P.; Wooster, R.; Anderson, D. G. The clinical progress of mRNA vaccines and immunotherapies. Nat. Biotechnol. 2022, 40, 840-54.

54. Shaw, C. A.; Essink, B.; Harper, C.; et al. Safety and immunogenicity of an mRNA-based RSV vaccine including a 12-month booster in a phase 1 clinical trial in healthy older adults. J. Infect. Dis. 2024, 230, e647-56.

55. Hanada, S.; Pirzadeh, M.; Carver, K. Y.; Deng, J. C. Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia. Front. Immunol. 2018, 9, 2640.

56. Maginnis, M. S. Virus-receptor interactions: the key to cellular invasion. J. Mol. Biol. 2018, 430, 2590-611.

57. Herold, S.; Becker, C.; Ridge, K. M.; Budinger, G. R. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur. Respir. J. 2015, 45, 1463-78.

58. Arevalo, C. P.; Bolton, M. J.; Le, S. V.; et al. A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science 2022, 378, 899-904.

59. Bahl, K.; Senn, J. J.; Yuzhakov, O.; et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol. Ther. 2017, 25, 1316-27.

60. Hou, X.; Zaks, T.; Langer, R.; Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 2021, 6, 1078-94.

61. Magini, D.; Giovani, C.; Mangiavacchi, S.; et al. Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLoS. One. 2016, 11, e0161193.

62. Lokugamage, M. P.; Vanover, D.; Beyersdorf, J.; et al. Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs. Nat. Biomed. Eng. 2021, 5, 1059-68.

63. Zhuang, X.; Chen, L.; Yang, S.; et al. R848 Adjuvant laden with self-assembled nanoparticle-based mRNA vaccine elicits protective immunity against H5N1 in mice. Front. Immunol. 2022, 13, 836274.

64. Jackson, C. B.; Farzan, M.; Chen, B.; Choe, H. Mechanisms of SARS-CoV-2 entry into cells. Nat. Rev. Mol. Cell. Biol. 2022, 23, 3-20.

65. Gusev, E.; Sarapultsev, A.; Solomatina, L.; Chereshnev, V. SARS-CoV-2-specific immune response and the pathogenesis of COVID-19. Int. J. Mol. Sci. 2022, 23, 1716.

66. Meo, S. A.; Bukhari, I. A.; Akram, J.; Meo, A. S.; Klonoff, D. C. COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and moderna vaccines. Eur. Rev. Med. Pharmacol. Sci. 2021, 25, 1663-9.

67. Khurana, A.; Allawadhi, P.; Khurana, I.; et al. Role of nanotechnology behind the success of mRNA vaccines for COVID-19. Nano. Today. 2021, 38, 101142.

68. Chen, K.; Fan, N.; Huang, H.; et al. mRNA vaccines against SARS-CoV-2 variants delivered by lipid nanoparticles based on novel ionizable lipids. Adv. Funct. Mater. 2022, 32, 2204692.

69. Venit, T.; Blavier, J.; Maseko, S. B.; et al. Nanobody against SARS-CoV-2 non-structural protein Nsp9 inhibits viral replication in human airway epithelia. Mol. Ther. Nucleic. Acids. 2024, 35, 102304.

70. Ma, Q.; Li, R.; Guo, J.; et al. Immunization with a prefusion SARS-CoV-2 spike protein vaccine (RBMRNA-176) protects against viral challenge in mice and nonhuman primates. Vaccines. (Basel). 2022, 10, 1698.

71. Tai, W.; Yang, K.; Liu, Y.; et al. A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection. Nat. Commun. 2023, 14, 8042.

72. Uraki, R.; Imai, M.; Ito, M.; et al. An mRNA vaccine encoding the SARS-CoV-2 receptor-binding domain protects mice from various Omicron variants. NPJ. Vaccines. 2024, 9, 4.

73. Li, J.; Xiao, L.; Chen, Z.; et al. A spike-based mRNA vaccine that induces durable and broad protection against porcine deltacoronavirus in piglets. J. Virol. 2024, 98, e0053524.

74. Kim, J.; Jozic, A.; Mukherjee, A.; et al. Rapid generation of circulating and mucosal decoy human ACE2 using mRNA nanotherapeutics for the potential treatment of SARS-CoV-2. Adv. Sci. (Weinh). 2022, 9, e2202556.

75. Milligan, E. C.; Olstad, K.; Williams, C. A.; et al. Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later. Sci. Transl. Med. 2023, 15, eadd6383.

76. Zhao, H.; Wang, T. C.; Li, X. F.; et al. Long-term stability and protection efficacy of the RBD-targeting COVID-19 mRNA vaccine in nonhuman primates. Signal. Transduct. Target. Ther. 2021, 6, 438.

77. Qin, J.; Jeon, J. H.; Xu, J.; et al. Design and preclinical evaluation of a universal SARS-CoV-2 mRNA vaccine. Front. Immunol. 2023, 14, 1126392.

78. Ye, Z.; Bonam, S. R.; McKay, L. G. A.; et al. Monovalent SARS-COV-2 mRNA vaccine using optimal UTRs and LNPs is highly immunogenic and broadly protective against Omicron variants. Proc. Natl. Acad. Sci. U. S. A. 2023, 120, e2311752120.

79. Polack, F. P.; Thomas, S. J.; Kitchin, N.; et al. C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N. Engl. J. Med. 2020, 383, 2603-15.

80. Baden, L. R.; El, S. H. M.; Essink, B.; et al. COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021, 384, 403-16.

81. Dagan, N.; Barda, N.; Kepten, E.; et al. BNT162b2 mRNA covid-19 vaccine in a nationwide mass vaccination setting. N. Engl. J. Med. 2021, 384, 1412-23.

82. Corbett, K. S.; Edwards, D. K.; Leist, S. R.; et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 2020, 586, 567-71.

83. Borchers, A. T.; Chang, C.; Gershwin, M. E.; Gershwin, L. J. Respiratory syncytial virus - a comprehensive review. Clin. Rev. Allergy. Immunol. 2013, 45, 331-79.

84. Garcia-Garcia, M. L.; Calvo, R. C.; Del, R. R. T. Pediatric asthma and viral infection. Arch. Bronconeumol. 2016, 52, 269-73.

85. Qiu, X.; Xu, S.; Lu, Y.; et al. Development of mRNA vaccines against respiratory syncytial virus (RSV). Cytokine. Growth. Factor. Rev. 2022, 68, 37-53.

86. Wu, N.; Zhang, J.; Shen, Y.; et al. A potential bivalent mRNA vaccine candidate protects against both RSV and SARS-CoV-2 infections. Mol. Ther. 2024, 32, 1033-47.

87. King, T. E. J.; Pardo, A.; Selman, M. Idiopathic pulmonary fibrosis. Lancet 2011, 378, 1949-61.

88. Eelen, G.; Treps, L.; Li, X.; Carmeliet, P. Basic and therapeutic aspects of angiogenesis updated. Circ. Res. 2020, 127, 310-29.

89. Popoola, D. O.; Cao, Z.; Men, Y.; et al. Lung-specific mRNA delivery enabled by sulfonium lipid nanoparticles. Nano. Lett. 2024, 24, 8080-8.

90. Liu, G. Y.; Budinger, G. R. S.; Dematte, J. E. Advances in the management of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis. BMJ. 2022, 377, e066354.

91. Martinez, F. J.; Collard, H. R.; Pardo, A.; et al. Idiopathic pulmonary fibrosis. Nat. Rev. Dis. Primers. 2017, 3, 17074.

92. Spagnolo, P.; Kropski, J. A.; Jones, M. G.; et al. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development. Pharmacol. Ther. 2021, 222, 107798.

93. Moss, B. J.; Ryter, S. W.; Rosas, I. O. Pathogenic mechanisms underlying idiopathic pulmonary fibrosis. Annu. Rev. Pathol. 2022, 17, 515-46.

94. Richeldi, L.; Collard, H. R.; Jones, M. G. Idiopathic pulmonary fibrosis. Lancet 2017, 389, 1941-52.

95. Massaro, M.; Wu, S.; Baudo, G.; et al. Lipid nanoparticle-mediated mRNA delivery in lung fibrosis. Eur. J. Pharm. Sci. 2023, 183, 106370.

96. Wang, Y.; Zhang, J.; Liu, Y.; et al. Realveolarization with inhalable mucus-penetrating lipid nanoparticles for the treatment of pulmonary fibrosis in mice. Sci. Adv. 2024, 10, eado4791.

97. Zhang, R.; Jing, W.; Chen, C.; et al. Inhaled mRNA Nanoformulation with biogenic ribosomal protein reverses established pulmonary fibrosis in a bleomycin-induced murine model. Adv. Mater. 2022, 34, e2107506.

98. Rajendran, P.; Rengarajan, T.; Thangavel, J.; et al. The vascular endothelium and human diseases. Int. J. Biol. Sci. 2013, 9, 1057-69.

99. Augustin, H. G.; Koh, G. Y. Organotypic vasculature: from descriptive heterogeneity to functional pathophysiology. Science 2017, 357, eaal2379.

100. Teijaro, J. R.; Walsh, K. B.; Cahalan, S.; et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011, 146, 980-91.

101. Radloff, K.; Gutbier, B.; Dunne, C. M.; et al. Cationic LNP-formulated mRNA expressing Tie2-agonist in the lung endothelium prevents pulmonary vascular leakage. Mol. Ther. Nucleic. Acids. 2023, 34, 102068.

102. Zhao, G.; Xue, L.; Weiner, A. I.; et al. TGF-βR2 signaling coordinates pulmonary vascular repair after viral injury in mice and human tissue. Sci. Transl. Med. 2024, 16, eadg6229.

103. McCarthy, C.; Gupta, N.; Johnson, S. R.; Yu, J. J.; McCormack, F. X. Lymphangioleiomyomatosis: pathogenesis, clinical features, diagnosis, and management. Lancet. Respir. Med. 2021, 9, 1313-27.

104. Barrera E, Mancheño Franch N, Vera-Sempere F, Padilla Alarcón J. Lymphangioleiomyomatosis. Arch. Bronconeumol. 2011, 47, 85-93.

105. Kundu, N.; Holz, M. K. Lymphangioleiomyomatosis: a metastatic lung disease. Am. J. Physiol. Cell. Physiol. 2023, 324, C320-6.

106. Bhaoighill, M. N.; Dunlop, E. A. Mechanistic target of rapamycin inhibitors: successes and challenges as cancer therapeutics. Cancer. Drug. Resist. 2019, 2, 1069-85.

107. Qiu, M.; Tang, Y.; Chen, J.; et al. Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis. Proc. Natl. Acad. Sci. U. S. A. 2022, 119.

108. Remark, R.; Becker, C.; Gomez, J. E.; et al. The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome. Am. J. Respir. Crit. Care. Med. 2015, 191, 377-90.

109. Jones, G. S.; Baldwin, D. R. Recent advances in the management of lung cancer. Clin. Med. (Lond). 2018, 18, s41-6.

110. Feng, J.; Zhang, P.; Wang, D.; Li, Y.; Tan, J. New strategies for lung cancer diagnosis and treatment: applications and advances in nanotechnology. Biomark. Res. 2024, 12, 136.

111. Cheng, X.; Liu, Q.; Li, H.; et al. Lipid nanoparticles loaded with an antisense oligonucleotide gapmer against Bcl-2 for treatment of lung cancer. Pharm. Res. 2017, 34, 310-20.

112. Cheng, X.; Yu, D.; Cheng, G.; et al. T7 Peptide-conjugated lipid nanoparticles for dual modulation of Bcl-2 and Akt-1 in lung and cervical carcinomas. Mol. Pharm. 2018, 15, 4722-32.

113. Yu, J.; Li, Q.; Zhang, C.; et al. Targeted LNPs deliver IL-15 superagonists mRNA for precision cancer therapy. Biomaterials 2025, 317, 123047.

114. Hussain, M. S.; Sultana, A.; Bisht, A. S.; Gupta, G. Groundbreaking mRNA lung cancer vaccine trials: a new dawn in cancer treatment. Curr. Cancer. Drug. Targets. , 2025, 1082-7.

115. Kon, E.; Ad-El, N.; Hazan-Halevy, I.; Stotsky-Oterin, L.; Peer, D. Targeting cancer with mRNA-lipid nanoparticles: key considerations and future prospects. Nat. Rev. Clin. Oncol. 2023, 20, 739-54.

116. Kiaie, S. H.; Majidi, Z. N.; Ahmadi, A.; et al. Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects. J. Nanobiotechnology. 2022, 20, 276.

117. Rospond, B.; Krakowska, A.; Muszyńska, B.; Opoka, W. The history, current state and perspectives of aerosol therapy. Acta. Pharm. 2022, 72, 225-43.

118. van, R. C. J. M.; Vlaming, K. E.; Bem, R. A.; et al. Low energy nebulization preserves integrity of SARS-CoV-2 mRNA vaccines for respiratory delivery. Sci. Rep. 2023, 13, 8851.

119. Yan, R.; Zou, C.; Yang, X.; et al. Nebulized inhalation drug delivery: clinical applications and advancements in research. J. Mater. Chem. B. 2025, 13, 821-43.

120. Miao, H.; Huang, K.; Li, Y.; et al. Optimization of formulation and atomization of lipid nanoparticles for the inhalation of mRNA. Int. J. Pharm. 2023, 640, 123050.

121. Kim, J.; Jozic, A.; Lin, Y.; et al. Engineering Lipid Nanoparticles for Enhanced Intracellular Delivery of mRNA through Inhalation. ACS. Nano. 2022, 16, 14792-806.

122. Jiang, A. Y.; Witten, J.; Raji, I. O.; et al. Combinatorial development of nebulized mRNA delivery formulations for the lungs. Nat. Nanotechnol. 2024, 19, 364-75.

123. Bai, X.; Chen, Q.; Li, F.; et al. Optimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy. Nat. Commun. 2024, 15, 6844.

124. Liu, S.; Wen, Y.; Shan, X.; et al. Charge-assisted stabilization of lipid nanoparticles enables inhaled mRNA delivery for mucosal vaccination. Nat. Commun. 2024, 15, 9471.

125. Courrier, H. M.; Butz, N.; Vandamme, T. F. Pulmonary drug delivery systems: recent developments and prospects. Crit. Rev. Ther. Drug. Carrier. Syst. 2002, 19, 425-98.

126. Molina, R. M.; Konduru, N. V.; Hirano, H.; et al. Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation. Inhal. Toxicol. 2016, 28, 550-60.

127. Wang, H.; Wu, L.; Sun, X. Intratracheal delivery of nano- and microparticles and hyperpolarized gases: a promising strategy for the imaging and treatment of respiratory disease. Chest 2020, 157, 1579-90.

128. Tafech, B.; Rokhforouz, M. R.; Leung, J.; et al. Exploring mechanisms of lipid nanoparticle-mucus interactions in healthy and cystic fibrosis conditions. Adv. Healthc. Mater. 2024, 13, e2304525.

129. Zhang, H.; Leal, J.; Soto, M. R.; Smyth, H. D. C.; Ghosh, D. Aerosolizable lipid nanoparticles for pulmonary delivery of mrna through design of experiments. Pharmaceutics 2020, 12, 1042.

130. Friis, K. P.; Gracin, S.; Oag, S.; et al. Spray dried lipid nanoparticle formulations enable intratracheal delivery of mRNA. J. Control. Release. 2023, 363, 389-401.

131. Sarode, A.; Patel, P.; Vargas-Montoya, N.; et al. Inhalable dry powder product (DPP) of mRNA lipid nanoparticles (LNPs) for pulmonary delivery. Drug. Deliv. Transl. Res. 2024, 14, 360-72.

132. Beck, S. E.; Laube, B. L.; Barberena, C. I.; et al. Deposition and expression of aerosolized rAAV vectors in the lungs of Rhesus macaques. Mol. Ther. 2002, 6, 546-54.

133. Pardi, N.; Tuyishime, S.; Muramatsu, H.; et al. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J. Control. Release. 2015, 217, 345-51.

134. Geng, L.; Kato, N.; Kodama, Y.; Mukai, H.; Kawakami, S. Influence of lipid composition of messenger RNA-loaded lipid nanoparticles on the protein expression via intratracheal administration in mice. Int. J. Pharm. 2023, 637, 122896.

135. Tam, A.; Kulkarni, J.; An, K.; et al. Lipid nanoparticle formulations for optimal RNA-based topical delivery to murine airways. Eur. J. Pharm. Sci. 2022, 176, 106234.

136. Loughrey, D.; Dahlman, J. E. Non-liver mRNA Delivery. Acc. Chem. Res. 2022, 55, 13-23.

137. Zhang, W.; Chetwynd, A. J.; Thorn, J. A.; Lynch, I.; Ramautar, R. Understanding the significance of sample preparation in studies of the nanoparticle metabolite corona. ACS. Meas. Sci. Au. 2022, 2, 251-60.

138. Ke, P. C.; Lin, S.; Parak, W. J.; Davis, T. P.; Caruso, F. A decade of the protein corona. ACS. Nano. 2017, 11, 11773-6.

139. Walczyk, D.; Bombelli, F. B.; Monopoli, M. P.; Lynch, I.; Dawson, K. A. What the cell “sees” in bionanoscience. J. Am. Chem. Soc. 2010, 132, 5761-8.

140. Lynch, I.; Dawson, K. A.; Linse, S. Detecting cryptic epitopes created by nanoparticles. Sci. STKE. 2006, 2006, pe14.

141. Monopoli, M. P.; Aberg, C.; Salvati, A.; Dawson, K. A. Biomolecular coronas provide the biological identity of nanosized materials. Nat. Nanotechnol. 2012, 7, 779-86.

142. Petersen, D. M. S.; Weiss, R. M.; Hajj, K. A.; et al. Branched-tail lipid nanoparticles for intravenous mRNA delivery to lung immune, endothelial, and alveolar cells in mice. Adv. Healthc. Mater. 2024, 13, e2400225.

143. Eygeris, Y.; Gupta, M.; Kim, J.; et al. Thiophene-based lipids for mRNA delivery to pulmonary and retinal tissues. Proc. Natl. Acad. Sci. U. S. A. 2024, 121, e2307813120.

144. Kim, M.; Jeong, M.; Lee, G.; et al. Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety. Bioeng. Transl. Med. 2023, 8, e10556.

145. Kowalski, P. S.; Capasso, P. U.; Huang, Y.; Rudra, A.; Langer, R.; Anderson, D. G. Ionizable amino-polyesters synthesized via ring opening polymerization of tertiary amino-alcohols for tissue selective mRNA delivery. Adv. Mater. 2018, e1801151.

146. Guéguen, C.; Ben, C. T.; Briand, M.; et al. Evaluating how cationic lipid affects mRNA-LNP physical properties and biodistribution. Eur. J. Pharm. Biopharm. 2024, 195, 114077.

147. Zeng, G.; He, Z.; Yang, H.; et al. Cationic lipid pairs enhance liver-to-lung tropism of lipid nanoparticles for in vivo mRNA delivery. ACS. Appl. Mater. Interfaces. 2024, 16, 25698-709.

148. Cheng, Q.; Wei, T.; Farbiak, L.; Johnson, L. T.; Dilliard, S. A.; Siegwart, D. J. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol. 2020, 15, 313-20.

149. Wei, T.; Sun, Y.; Cheng, Q.; et al. Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models. Nat. Commun. 2023, 14, 7322.

150. Dabke, A.; Ghosh, S.; Dabke, P.; Sawant, K.; Khopade, A. Revisiting the in-vitro and in-vivo considerations for in-silico modelling of complex injectable drug products. J. Control. Release. 2023, 360, 185-211.

151. Sun, Y.; Chatterjee, S.; Lian, X.; et al. In vivo editing of lung stem cells for durable gene correction in mice. Science 2024, 384, 1196-202.

152. Dilliard, S. A.; Cheng, Q.; Siegwart, D. J. On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles. Proc. Natl. Acad. Sci. U. S. A. 2021, 118.

153. Vayalakkara, R. K.; Lo, C. L.; Chen, H. H.; et al. Photothermal/NO combination therapy from plasmonic hybrid nanotherapeutics against breast cancer. J. Control. Release. 2022, 345, 417-32.

154. Radmand, A.; Kim, H.; Beyersdorf, J.; et al. Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart. Proc. Natl. Acad. Sci. U. S. A. 2024, 121, e2307801120.

155. Fei, Y.; Yu, X.; Liu, P.; Ren, H.; Wei, T.; Cheng, Q. Simplified lipid nanoparticles for tissue- and cell-targeted mRNA delivery facilitate precision tumor therapy in a lung metastasis mouse model. Adv. Mater. 2024, 36, e2409812.

156. Tkachenko, E.; Tse, D.; Sideleva, O.; et al. Caveolae, fenestrae and transendothelial channels retain PV1 on the surface of endothelial cells. PLoS. One. 2012, 7, e32655.

157. Parton, R. G.; del, P. M. A. Caveolae as plasma membrane sensors, protectors and organizers. Nat. Rev. Mol. Cell. Biol. 2013, 14, 98-112.

158. Li, Q.; Chan, C.; Peterson, N.; et al. Engineering caveolae-targeted lipid nanoparticles to deliver mRNA to the lungs. ACS. Chem. Biol. 2020, 15, 830-6.

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