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REVIEW

Opportunities and Challenges for Inhalable Nanomedicine Formulations in Respiratory Diseases: A Review

, , , , &
Pages 1509-1538 | Received 09 Nov 2023, Accepted 24 Jan 2024, Published online: 16 Feb 2024

References

  • Hayes AJ, Bakand S. Toxicological perspectives of inhaled therapeutics and nanoparticles. Expert Opin Drug Metab Toxicol. 2014;10(7):933–947. doi:10.1517/17425255.2014.916276
  • Hye T, Moinuddin SM, Sarkar T, Nguyen T, Saha D, Ahsan F. An evolving perspective on novel modified release drug delivery systems for inhalational therapy. Expert Opin Drug Delivery. 2023;20(3):335–348. doi:10.1080/17425247.2023.2175814
  • Forest V, Pourchez J. Nano-delivery to the lung - by inhalation or other routes and why nano when micro is largely sufficient? Adv Drug Deliv Rev. 2022;183:114173.
  • Zhang YB, Xu D, Bai L, Zhou YM, Zhang H, Cui YL. A review of non-invasive drug delivery through respiratory routes. Pharmaceutics. 2022;14:9. doi:10.3390/pharmaceutics14091974
  • Kamat S, Kumari M, Jayabaskaran C. Nano-engineered tools in the diagnosis, therapeutics, prevention, and mitigation of SARS-CoV-2. J Cont Rel. 2021;338:813–836. doi:10.1016/j.jconrel.2021.08.046
  • Xi J, Longest PW, Martonen TB. Effects of the laryngeal jet on nano- and microparticle transport and deposition in an approximate model of the upper tracheobronchial airways. J Appl Physiol. 2008;104(6):1761–1777. doi:10.1152/japplphysiol.01233.2007
  • Sreedharan S, Zouganelis G, Drake SJ, Tripathi G, Kermanizadeh A. Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions. J Toxicol Env Heal B. 2023;26(1):1–27. doi:10.1080/10937404.2022.2153456
  • Bock S, Rades T, Rantanen J, Scherließ R. Additive manufacturing in respiratory sciences - Current applications and future prospects. Adv. Drug Delivery Rev. 2022;186:114341. doi:10.1016/j.addr.2022.114341
  • Mrsny RJ. Lessons from nature: ”Pathogen-Mimetic” systems for mucosal nano-medicines. Adv Drug Deliv Rev. 2009;61(2):172–192.
  • Nho R. Pathological effects of nano-sized particles on the respiratory system. Nanomedicine. 2020;29:102242. doi:10.1016/j.nano.2020.102242
  • Xing Y, Lu P, Xue Z, et al. Nano-strategies for improving the bioavailability of inhaled pharmaceutical formulations. Mini Rev Med Chem. 2020;20(13):1258–1271. doi:10.2174/1389557520666200509235945
  • Zhao Q, Li Y, Chai X, et al. Interaction of pulmonary surfactant with silica and polycyclic aromatic hydrocarbons: implications for respiratory health. Chemosphere. 2019;222:603–610. doi:10.1016/j.chemosphere.2019.02.002
  • Seyfoori A, Shokrollahi Barough M, Mokarram P, et al. Emerging advances of nanotechnology in drug and vaccine delivery against viral associated respiratory infectious diseases (VARID). Int J Mol Sci. 2021;22:13. doi:10.3390/ijms22136937
  • Xu Y, Parra-Ortiz E, Wan F, et al. Insights into the mechanisms of interaction between inhalable lipid-polymer hybrid nanoparticles and pulmonary surfactant. J Colloid Interface Sci. 2023;633:511–525. doi:10.1016/j.jcis.2022.11.059
  • Zhao J, Su J, Qin L, Zhang X, Mao S. Exploring the influence of inhaled liposome membrane fluidity on its interaction with pulmonary physiological barriers. Biomater Sci. 2020;8(23):6786–6797. doi:10.1039/D0BM01529F
  • Ali ME, McConville JT, Lamprecht A. Pulmonary delivery of anti-inflammatory agents. Expert Opin Drug Deliv. 2015;12(6):929–945. doi:10.1517/17425247.2015.993968
  • Renwick LC, Donaldson K, Clouter A. Impairment of alveolar macrophage phagocytosis by ultrafine particles. Toxicol Appl Pharmacol. 2001;172(2):119–127. doi:10.1006/taap.2001.9128
  • Zhang Y, Wong CYJ, Gholizadeh H, et al. Microfluidics assembly of inhalable liposomal ciprofloxacin characterised by an innovative in vitro pulmonary model. Int J Pharm. 2023;635:122667. doi:10.1016/j.ijpharm.2023.122667
  • Gradon L, Orlicki D, Podgorski A. Deposition and retention of ultrafine aerosol particles in the human respiratory system. Normal and pathological cases. Int J Occup Saf Ergon. 2000;6(2):189–207. doi:10.1080/10803548.2000.11076451
  • Stone V, Johnston H, Clift MJ. Air pollution, ultrafine and nanoparticle toxicology: cellular and molecular interactions. IEEE Trans NanoBiosci. 2007;6(4):331–340. doi:10.1109/TNB.2007.909005
  • Kwok PC, Tunsirikongkon A, Glover W, Chan HK. Formation of protein nano-matrix particles with controlled surface architecture for respiratory drug delivery. Pharm Res. 2011;28(4):788–796. doi:10.1007/s11095-010-0332-2
  • Poh TY, Ali N, Mac Aogáin M, et al. Inhaled nanomaterials and the respiratory microbiome: clinical, immunological and toxicological perspectives. Part Fibre Toxicol. 2018;15(1):46.
  • Wang W, Huang Z, Huang Y, et al. Pulmonary delivery nanomedicines towards circumventing physiological barriers: strategies and characterization approaches. Adv. Drug Delivery Rev. 2022;185:114309. doi:10.1016/j.addr.2022.114309
  • Fornaguera C, Llinas M, Solans C, Caldero G. Design and in vitro evaluation of biocompatible dexamethasone-loaded nanoparticle dispersions, obtained from nano-emulsions, for inhalatory therapy. Colloids Surf B Biointerfaces. 2015;125:58–64. doi:10.1016/j.colsurfb.2014.11.006
  • Ziaei E, Emami J, Rezazadeh M, Kazemi M. Pulmonary delivery of docetaxel and celecoxib by PLGA porous microparticles for their synergistic effects against lung cancer. Anticancer Agents Med Chem. 2022;22(5):951–967. doi:10.2174/1871520621666210811111152
  • Rashid J, Alobaida A, Al-Hilal TA, et al. Repurposing rosiglitazone, a PPAR-gamma agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH. J Control Release. 2018;280:113–123.
  • Rasul RM, Tamilarasi Muniandy M, Zakaria Z, et al. A review on chitosan and its development as pulmonary particulate anti-infective and anti-cancer drug carriers. Carbohydr Polym. 2020;250:116800.
  • Paul P, Sengupta S, Mukherjee B, Shaw TK, Gaonkar RH, Debnath MC. Chitosan-coated nanoparticles enhanced lung pharmacokinetic profile of voriconazole upon pulmonary delivery in mice. Nanomedicine (Lond). 2018;13(5):501–520. doi:10.2217/nnm-2017-0291
  • Bandi N, Ayalasomayajula SP, Dhanda DS, Iwakawa J, Cheng PW, Kompella UB. Intratracheal budesonide-poly(lactide-co-glycolide) microparticles reduce oxidative stress, VEGF expression, and vascular leakage in a benzo(a)pyrene-fed mouse model. J Pharm Pharmacol. 2005;57(7):851–860. doi:10.1211/0022357056334
  • Yoo D, Guk K, Kim H, Khang G, Wu D, Lee D. Antioxidant polymeric nanoparticles as novel therapeutics for airway inflammatory diseases. Int J Pharm. 2013;450(1–2):87–94. doi:10.1016/j.ijpharm.2013.04.028
  • Satta S, Shahabipour F, Gao W, et al. Engineering viral genomics and nano-liposomes in microfluidic platforms for patient-specific analysis of SARS-CoV-2 variants. Theranostics. 2022;12(10):4779–4790. doi:10.7150/thno.72339
  • LoPresti ST, Arral ML, Chaudhary N, Whitehead KA. The replacement of helper lipids with charged alternatives in lipid nanoparticles facilitates targeted mRNA delivery to the spleen and lungs. J Cont Rel. 2022;345:819–831. doi:10.1016/j.jconrel.2022.03.046
  • Weber S, Zimmer A, Pardeike J. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for pulmonary application: a review of the state of the art. Eur J Pharm Biopharm. 2014;86(1):7–22. doi:10.1016/j.ejpb.2013.08.013
  • Nahar K, Absar S, Patel B, Ahsan F. Starch-coated magnetic liposomes as an inhalable carrier for accumulation of fasudil in the pulmonary vasculature. Int J Pharm. 2014;464(1–2):185–195. doi:10.1016/j.ijpharm.2014.01.007
  • Rashid J, Nahar K, Raut S, Keshavarz A, Ahsan F. Fasudil and DETA NONOate, loaded in a peptide-modified liposomal carrier, Slow PAH progression upon pulmonary delivery. Mol Pharm. 2018;15(5):1755–1765. doi:10.1021/acs.molpharmaceut.7b01003
  • Garbuzenko OB, Kuzmov A, Taratula O, Pine SR, Minko T. Strategy to enhance lung cancer treatment by five essential elements: inhalation delivery, nanotechnology, tumor-receptor targeting, chemo- and gene therapy. Theranostics. 2019;9(26):8362–8376. doi:10.7150/thno.39816
  • Jiang Z, Ma Y, Guo X, et al. Sustainable production of lignin micro-/nano-particles (LMNPs) from biomass: influence of the type of biomass on their self-assembly capability and physicochemical properties. J Hazard Mater. 2021;403:123701. doi:10.1016/j.jhazmat.2020.123701
  • Sakellari GI, Zafeiri I, Batchelor H, Spyropoulos F. Formulation design, production and characterisation of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the encapsulation of a model hydrophobic active. Food Hydrocoll Health. 2021;2021:1.
  • Khan I, Hussein S, Houacine C, et al. Fabrication, characterization and optimization of nanostructured lipid carrier formulations using Beclomethasone dipropionate for pulmonary drug delivery via medical nebulizers. Int J Pharm. 2021;598:120376. doi:10.1016/j.ijpharm.2021.120376
  • Prasanna P, Rathee S, Upadhyay A, Sulakshana S. Nanotherapeutics in the treatment of acute respiratory distress syndrome. Life Sci. 2021;276:119428. doi:10.1016/j.lfs.2021.119428
  • Li H, Sun J, Zhu H, et al. Recent advances in development of dendritic polymer-based nanomedicines for cancer diagnosis. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021;13(2):e1670. doi:10.1002/wnan.1670
  • Halevas E, Mavroidi B, Kokotidou C, et al. Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery. J Drug Deliv Sci Technol. 2022;75:103625. doi:10.1016/j.jddst.2022.103625
  • Kaminskas LM, McLeod VM, Ryan GM, et al. Pulmonary administration of a doxorubicin-conjugated dendrimer enhances drug exposure to lung metastases and improves cancer therapy. J Control Release. 2014;183:18–26. doi:10.1016/j.jconrel.2014.03.012
  • Zamborlin A, Ermini ML, Summa M, et al. The fate of intranasally instilled silver nanoarchitectures. Nano Lett. 2022;22(13):5269–5276. doi:10.1021/acs.nanolett.2c01180
  • Tseng CL, Su WY, Yen KC, Yang KC, Lin FH. The use of biotinylated-EGF-modified gelatin nanoparticle carrier to enhance cisplatin accumulation in cancerous lungs via inhalation. Biomaterials. 2009;30(20):3476–3485. doi:10.1016/j.biomaterials.2009.03.010
  • Hindi KM, Ditto AJ, Panzner MJ, et al. The antimicrobial efficacy of sustained release silver-carbene complex-loaded L-tyrosine polyphosphate nanoparticles: characterization, in vitro and in vivo studies. Biomaterials. 2009;30(22):3771–3779. doi:10.1016/j.biomaterials.2009.03.044
  • Javed H, Shah SNH, Iqbal FM, Javed N, Saeed B. A hematological and histopathological study on diphenhydramine nasal nano-gel and nano-emulgel for the management of allergic rhinitis in animal model. AAPS Pharm Sci Tech. 2023;24(2):55. doi:10.1208/s12249-023-02515-w
  • Li Y, Han M, Liu T, Cun D, Fang L, Yang M. Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator. Carbohydr Polym. 2017;172:197–204. doi:10.1016/j.carbpol.2017.05.020
  • Yue P, Zhou W, Huang G, et al. Nanocrystals based pulmonary inhalation delivery system: advance and challenge. Drug Deliv. 2022;29(1):637–651. doi:10.1080/10717544.2022.2039809
  • Costabile G, Provenzano R, Azzalin A, et al. PEGylated mucus-penetrating nanocrystals for lung delivery of a new FtsZ inhibitor against Burkholderia cenocepacia infection. Nanomedicine. 2020;23:102113. doi:10.1016/j.nano.2019.102113
  • Ju Y, Hu Y, Yang P, Xie X, Fang B. Extracellular vesicle-loaded hydrogels for tissue repair and regeneration. Mater Today Bio. 2023;2023:18.
  • Popowski KD, Moatti A, Scull G, et al. Inhalable dry powder mRNA vaccines based on extracellular vesicles. Matter. 2022;5(9):2960–2974. doi:10.1016/j.matt.2022.06.012
  • Han Y, Zhu Y, Youngblood HA, et al. Nebulization of extracellular vesicles: a promising small RNA delivery approach for lung diseases. J Control Release. 2022;352:556–569. doi:10.1016/j.jconrel.2022.10.052
  • Zhai Z, Cui T, Chen J, Mao X, Zhang T. Advancements in engineered mesenchymal stem cell exosomes for chronic lung disease treatment. J Transl Med. 2023;21(1). doi:10.1186/s12967-023-04729-9
  • Liu C, Xi L, Liu Y, et al. An inhalable hybrid biomimetic nanoplatform for sequential drug release and remodeling lung immune homeostasis in acute lung injury treatment. ACS Nano. 2023;17(12):11626–11644. doi:10.1021/acsnano.3c02075
  • Rothen DA, Krenger PS, Nonic A, et al. Intranasal administration of a virus like particles‐based vaccine induces neutralizing antibodies against SARS‐CoV‐2 and variants of concern. Allergy. 2022;77(8):2446–2458. doi:10.1111/all.15311
  • Wang Z, Popowski KD, Zhu D, et al. Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine. Nat Biomed Eng. 2022;6(7):791–805. doi:10.1038/s41551-022-00902-5
  • Zakaria MY, El-Halim SM A, Beshay BY, Zaki I, Abourehab MAS. ‘Poly phenolic phytoceutical loaded nano-bilosomes for enhanced caco-2 cell permeability and SARS-CoV 2 antiviral activity’: in-vitro and insilico studies. Drug Deliv. 2023;30(1):2162157. doi:10.1080/10717544.2022.2162157
  • Detalle L, Stohr T, Palomo C, et al. Generation and characterization of ALX-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection. Antimicrob Agents Chemother. 2016;60(1):6–13. doi:10.1128/AAC.01802-15
  • Liu Q, Guan J, Song R, Zhang X, Mao S. Physicochemical properties of nanoparticles affecting their fate and the physiological function of pulmonary surfactants. Acta Biomater. 2022;140:76–87. doi:10.1016/j.actbio.2021.11.034
  • Raine RI. Technology in respiratory medicine. Cont Med Educ. 2003;16(4):200.
  • Barthold S, Kunschke N, Murgia X, Loretz B, Carvalho-Wodarz CS, Lehr CM. Overview of inhaled nanopharmaceuticals. J Aerosol Med Pulm Drug Deliv. 2023;36(3):144–151. doi:10.1089/jamp.2023.29089.sb
  • Chen C, Zhou C, Zhang W, et al. Effect and mechanism of PINK1/parkin-mediated mitochondrial autophagy in rat lung injury induced by nano lanthanum oxide. Nanomaterials. 2022;12:15.
  • Basu S, Kabi P, Chaudhuri S, Saha A. Insights on drying and precipitation dynamics of respiratory droplets from the perspective of COVID-19. Phys Fluids. 2020;32(12):123317. doi:10.1063/5.0037360
  • Fdez-Arroyabe P, Salcines C, Kassomenos P, Santurtún A, Petäjä T. Electric charge of atmospheric nanoparticles and its potential implications with human health. Sci Total Environ. 2022;808:152106. doi:10.1016/j.scitotenv.2021.152106
  • Phan TH, Shi H, Denes CE, et al. Advanced pathophysiology mimicking lung models for accelerated drug discovery. Biomater Res. 2023;27(1):35. doi:10.1186/s40824-023-00366-x
  • 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(6):1579–1590. doi:10.1016/j.chest.2019.11.036
  • Blank F, Fytianos K, Seydoux E, et al. Interaction of biomedical nanoparticles with the pulmonary immune system. J Nanobiotechnology. 2017;15(1):6. doi:10.1186/s12951-016-0242-5
  • Ruenraroengsak P, Novak P, Berhanu D, et al. Respiratory epithelial cytotoxicity and membrane damage (holes) caused by amine-modified nanoparticles. Nanotoxicology. 2012;6(1):94–108. doi:10.3109/17435390.2011.558643
  • Doryab A, Taskin MB, Stahlhut P, et al. A bioinspired in vitro lung model to study particokinetics of nano-/microparticles under cyclic stretch and air-liquid interface conditions. Front Bioeng Biotechnol. 2021;9:616830. doi:10.3389/fbioe.2021.616830
  • Bessa MJ, Brandão F, Rosário F, et al. Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models. J Toxicol Env Heal B. 2023;26(2):67–96. doi:10.1080/10937404.2023.2166638
  • Geiser M, Kreyling WG. Deposition and biokinetics of inhaled nanoparticles. Part Fibre Toxicol. 2010;7:2. doi:10.1186/1743-8977-7-2
  • Kurbatova P, Bessonov N, Volpert V, et al. Model of mucociliary clearance in cystic fibrosis lungs. J Theor Biol. 2015;372:81–88. doi:10.1016/j.jtbi.2015.02.023
  • Bustamante-Marin XM, Ostrowski LE. Cilia and mucociliary clearance. Cold Spring Harbor Perspect. Biol. 2017;9(4):a028241. doi:10.1101/cshperspect.a028241
  • Newman SP. Drug delivery to the lungs: challenges and opportunities. Therap Deliv. 2017;8(8):647–661. doi:10.4155/tde-2017-0037
  • Anderson CF, Grimmett ME, Domalewski CJ, Cui H. Inhalable nanotherapeutics to improve treatment efficacy for common lung diseases. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020;12:1.
  • Kiyono H, Azegami T. The mucosal immune system: from dentistry to vaccine development. Proc Jpn Acad Ser B Phys Biol Sci. 2015;91(8):423–439. doi:10.2183/pjab.91.423
  • Ardain A, Marakalala MJ, Leslie A. Tissue-resident innate immunity in the lung. Immunology. 2020;159(3):245–256. doi:10.1111/imm.13143
  • Gosens I, Cassee FR, Zanella M, et al. Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure. Nanotoxicology. 2016;10(8):1084–1095. doi:10.3109/17435390.2016.1172678
  • Patton JS, Brain JD, Davies LA, et al. The particle has landed--characterizing the fate of inhaled pharmaceuticals. J Aero Med Pulm Drug Deliv. 2010;23:S71–87.
  • Mühlfeld C, Rothen-Rutishauser B, Blank F, Vanhecke D, Ochs M, Gehr P. Interactions of nanoparticles with pulmonary structures and cellular responses. Am J Physiol Lung Cell Mol Physiol. 2008;294(5):L817–829. doi:10.1152/ajplung.00442.2007
  • Truzzi E, Nascimento TL, Iannuccelli V, et al. In vivo biodistribution of respirable solid lipid nanoparticles surface-decorated with a mannose-based surfactant: a promising tool for pulmonary tuberculosis treatment? Nanomaterials. 2020;10:3.
  • Shah RM, Rajasekaran D, Ludford-Menting M, Eldridge DS, Palombo EA, Harding IH. Transport of stearic acid-based solid lipid nanoparticles (SLNs) into human epithelial cells. Colloids Surf B. 2016;140:204–212. doi:10.1016/j.colsurfb.2015.12.029
  • Guagliardo R, Pérez-Gil J, De Smedt S, Raemdonck K. Pulmonary surfactant and drug delivery: focusing on the role of surfactant proteins. J Cont Rel. 2018;291:116–126. doi:10.1016/j.jconrel.2018.10.012
  • Vega-Villa KR, Takemoto JK, Yáñez JA, Remsberg CM, Forrest ML, Davies NM. Clinical toxicities of nanocarrier systems. Adv Drug Deliv Rev. 2008;60(8):929–938. doi:10.1016/j.addr.2007.11.007
  • Soto KF, Murr LE, Garza KM. Cytotoxic responses and potential respiratory health effects of carbon and carbonaceous nanoparticulates in the Paso del Norte airshed environment. Int J Environ Res Public Health. 2008;5(1):12–25. doi:10.3390/ijerph5010012
  • Cena LG, Chisholm WP, Keane MJ, Chen BT. A field study on the respiratory deposition of the nano-sized fraction of mild and stainless steel welding fume metals. J Occup Environ Hyg. 2015;12(10):721–728. doi:10.1080/15459624.2015.1043055
  • Bierkandt FS, Leibrock L, Wagener S, Laux P, Luch A. The impact of nanomaterial characteristics on inhalation toxicity. Toxicol Res (Camb). 2018;7(3):321–346.
  • Song S, Ding L, Liu G, et al. The protective effects of baicalin for respiratory diseases: an update and future perspectives. Front Pharmacol. 2023;14:1129817.
  • Lee SH, Wang TY, Hong JH, Cheng TJ, Lin CY. NMR-based metabolomics to determine acute inhalation effects of nano- and fine-sized ZnO particles in the rat lung. Nanotoxicology. 2016;10(7):924–934.
  • Dobson J. Toxicological aspects and applications of nanoparticles in paediatric respiratory disease. Paediatr Respir Rev. 2007;8(1):62–66.
  • Li Y, Zhu Y, Zhao B, et al. Amorphous silica nanoparticles caused lung injury through the induction of epithelial apoptosis via ROS/Ca(2+)/DRP1-mediated mitochondrial fission signaling. Nanotoxicology. 2022;16:6–8.
  • Sayers BC, Germolec DR, Walker NJ, et al. Respiratory toxicity and immunotoxicity evaluations of microparticle and nanoparticle C60 fullerene aggregates in mice and rats following nose-only inhalation for 13 weeks. Nanotoxicology. 2016;10(10):1458–1468.
  • Sun D, Zhang G, Xie M, et al. Softness enhanced macrophage-mediated therapy of inhaled apoptotic-cell-inspired nanosystems for acute lung injury. J Nanobiotechnology. 2023;21(1):172.
  • Wei T, Tang M. Biological effects of airborne fine particulate matter (PM(2.5)) exposure on pulmonary immune system. Environ Toxicol Pharmacol. 2018;60:195–201.
  • Yu Y, Pan Y, Chang B, Zhao X, Qu K, Song Y. Silica nanoparticles induce pulmonary damage in rats via VEGFC/D-VEGFR3 signaling-mediated lymphangiogenesis and remodeling. Toxicology. 2023;493:153552.
  • Lee SH, Tang CH, Lin WY, et al. LC-MS-based lipidomics to examine acute rat pulmonary responses after nano- and fine-sized ZnO particle inhalation exposure. Nanotoxicology. 2018;12(5):439–452.
  • Meneses J, González-Durruthy M, Fernandez-de-Gortari E, Toropova AP, Toropov AA, Alfaro-Moreno E. A Nano-QSTR model to predict nano-cytotoxicity: an approach using human lung cells data. Part Fibre Toxicol. 2023;20(1):21.
  • Yusuf A, Almotairy ARZ, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as drug delivery systems: a review of the implication of nanoparticles’ physicochemical properties on responses in biological systems. Polymers. 2023;15:7.
  • Huang X, Li C, Wei T, et al. Oropharyngeal aspirated Ag/TiO2 nanohybrids: transformation, distribution and toxicity. Science of the Total Environment. 2024;2024:908.
  • Tomita Y, Rikimaru-Kaneko A, Hashiguchi K, Shirotake S. Effect of anionic and cationic n-butylcyanoacrylate nanoparticles on NO and cytokine production in Raw264.7 cells. Immuno and Immunotoxicology. 2011;33(4):730–737. doi:10.3109/08923973.2011.565345
  • Xu Y, Zheng Y, Ding X, et al. PEGylated pH-responsive peptide-mRNA nano self-assemblies enhance the pulmonary delivery efficiency and safety of aerosolized mRNA. Drug Delivery. 2023;30(1):2219870. doi:10.1080/10717544.2023.2219870
  • Doroudian M, ON A, Mac Loughlin R, Prina-Mello A, Volkov Y, Donnelly SC. Nanotechnology in pulmonary medicine. Curr Opin Pharmacol. 2021;56:85–92. doi:10.1016/j.coph.2020.11.002
  • Omlor AJ, Nguyen J, Bals R, Dinh QT. Nanotechnology in respiratory medicine. Respir Res. 2015;16(1):64. doi:10.1186/s12931-015-0223-5
  • Doroudian M, MacLoughlin R, Poynton F, Prina-Mello A, Donnelly SC. Nanotechnology based therapeutics for lung disease. Thorax. 2019;74(10):965–976. doi:10.1136/thoraxjnl-2019-213037
  • Shim MK, Song SK, Jeon SI, Hwang KY, Kim K. Nano-sized drug delivery systems to potentiate the immune checkpoint blockade therapy. Expert Opin Drug Deliv. 2022;19(6):641–652. doi:10.1080/17425247.2022.2081683
  • Lee HY, Mohammed KA, Nasreen N. Nanoparticle-based targeted gene therapy for lung cancer. Am J Can Res. 2016;6(5):1118–1134.
  • Wang Y, Li S, Wang X, et al. Smart transformable nanomedicines for cancer therapy. Biomaterials. 2021;271:120737. doi:10.1016/j.biomaterials.2021.120737
  • Danhier F. To exploit the tumor microenvironment: since the EPR effect fails in the clinic, what is the future of nanomedicine? J Control Release. 2016;244(Pt A):108–121. doi:10.1016/j.jconrel.2016.11.015
  • Alshammari MK, Almomen EY, Alshahrani KF, et al. Nano-enabled strategies for the treatment of lung cancer: potential bottlenecks and future perspectives. Biomedicines. 2023;11(2). doi:10.3390/biomedicines11020473
  • Yang SJ, Huang CH, Wang CH, Shieh MJ, Chen KC. The synergistic effect of hyperthermia and chemotherapy in magnetite nanomedicine-based lung cancer treatment. Int j Nanomed. 2020;15:10331–10347. doi:10.2147/IJN.S281029
  • Guan S, Munder A, Hedtfeld S, et al. Self-assembled peptide-poloxamine nanoparticles enable in vitro and in vivo genome restoration for cystic fibrosis. Nat Nanotechnol. 2019;14(3):287–297. doi:10.1038/s41565-018-0358-x
  • Kuzmov A, Minko T. Nanotechnology approaches for inhalation treatment of lung diseases. J Control Release. 2015;219:500–518. doi:10.1016/j.jconrel.2015.07.024
  • Taratula O, Kuzmov A, Shah M, Garbuzenko OB, Minko T. Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA. J Control Release. 2013;171(3):349–357. doi:10.1016/j.jconrel.2013.04.018
  • Tian X, Gu T, Lee MH, Dong Z. Challenge and countermeasures for EGFR targeted therapy in non-small cell lung cancer. Biochim Biophys Acta Rev Cancer. 2022;1877(1):188645. doi:10.1016/j.bbcan.2021.188645
  • Tseng CL, Wu SY, Wang WH, et al. Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer. Biomaterials. 2008;29(20):3014–3022. doi:10.1016/j.biomaterials.2008.03.033
  • Sadhukha T, Wiedmann TS, Panyam J. Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy. Biomaterials. 2013;34(21):5163–5171. doi:10.1016/j.biomaterials.2013.03.061
  • Griesenbach U, Pytel KM, Alton EW. Cystic fibrosis gene therapy in the UK and elsewhere. Hum Gene Ther. 2015;26(5):266–275. doi:10.1089/hum.2015.027
  • Suk JS, Kim AJ, Trehan K, et al. Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier. J Control Release. 2014;178:8–17. doi:10.1016/j.jconrel.2014.01.007
  • Konstan MW, Davis PB, Wagener JS, 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(12):1255–1269. doi:10.1089/hum.2004.15.1255
  • Garbuzenko OB, Kbah N, Kuzmov A, Pogrebnyak N, Pozharov V, Minko T. Inhalation treatment of cystic fibrosis with lumacaftor and ivacaftor co-delivered by nanostructured lipid carriers. J Control Release. 2019;296:225–231.
  • Holgate ST, Wenzel S, Postma DS, Weiss ST, Renz H, Sly PD. Asthma. Nat Rev Dis Primers. 2015;1(1):15025.
  • Broza YY, Haick H. Nanomaterial-based sensors for detection of disease by volatile organic compounds. Nanomed. 2013;8(5):785–806. doi:10.2217/nnm.13.64
  • Taylor SL, Leong LEX, Choo JM, et al. Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology. J Allergy Clin Immunol. 2018;141(1):94–103.e115. doi:10.1016/j.jaci.2017.03.044
  • Plaza V, Crespo A, Giner J, et al. Inflammatory asthma phenotype discrimination using an electronic nose breath analyzer. J Investig Allergol Clin Immunol. 2015;25(6):431–437.
  • Craparo EF, Drago SE, Quaglia F, Ungaro F, Cavallaro G. Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation. Drug Delivery Transl Res. 2022;12(8):1859–1872. doi:10.1007/s13346-021-01102-5
  • Xu J, Xiao N, Zhou D, Xie L. Disease tolerance: a protective mechanism of lung infections. Front Cell Infect Microbiol. 2023;13:1037850. doi:10.3389/fcimb.2023.1037850
  • Pettigrew MM, Tanner W, Harris AD. The lung microbiome and pneumonia. J Infect Dis. 2021;223(12 Suppl 2):S241–s245. doi:10.1093/infdis/jiaa702
  • Zhang H, Zhang Y, Wu J, et al. Risks and features of secondary infections in severe and critical ill COVID-19 patients. Emerg Microbes Infect. 2020;9(1):1958–1964.
  • Vij N, Chandramani-Shivalingappa P, Van Westphal C, Hole R, Bodas M. Cigarette smoke-induced autophagy impairment accelerates lung aging, COPD-emphysema exacerbations and pathogenesis. Am J Physiol Cell Physiol. 2018;314(1):C73–C87. doi:10.1152/ajpcell.00110.2016
  • Costabile G, Mitidieri E, Visaggio D, et al. Boosting lung accumulation of gallium with inhalable nano-embedded microparticles for the treatment of bacterial pneumonia. Int J Pharm. 2022;629:122400. doi:10.1016/j.ijpharm.2022.122400
  • Costa-Gouveia J, Pancani E, Jouny S, et al. Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles. Sci Rep. 2017;7(1):5390. doi:10.1038/s41598-017-05453-3
  • Huck BC, Thiyagarajan D, Bali A, et al. Nano-in-microparticles for aerosol delivery of antibiotic-loaded, fucose-derivatized, and macrophage-targeted liposomes to combat mycobacterial infections: in vitro deposition, pulmonary barrier interactions, and targeted delivery. Adv. Healthcare Mater. 2022;11(11):e2102117. doi:10.1002/adhm.202102117
  • Tsoras AN, Champion JA. Protein and Peptide Biomaterials for Engineered Subunit Vaccines and Immunotherapeutic Applications. Annu Rev Chem Biomol. 2019;10:337–359. doi:10.1146/annurev-chembioeng-060718-030347
  • Loo CY, Lee WH, Zhou QT. Recent advances in inhaled nanoformulations of vaccines and therapeutics targeting respiratory viral infections. Pharm Res. 2023;40(5):1015–1036.
  • Zhong W, Zhang X, Zeng Y, Lin D, Wu J. Recent applications and strategies in nanotechnology for lung diseases. Nano Res. 2021;14(7):2067–2089.
  • Liu H, Moynihan KD, Zheng Y, et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature. 2014;507(7493):519–522. doi:10.1038/nature12978
  • Pati R, Shevtsov M, Sonawane A. Nanoparticle vaccines against infectious diseases. Front Immunol. 2018;9:2224.
  • Al-Halifa S, Gauthier L, Arpin D, Bourgault S, Archambault D. Nanoparticle-based vaccines against respiratory viruses. Front Immunol. 2019;10:22. doi:10.3389/fimmu.2019.00022
  • Sahin U, Türeci Ö. Personalized vaccines for cancer immunotherapy. Science. 2018;359(6382):1355–1360. doi:10.1126/science.aar7112
  • Vermaelen K. Vaccine strategies to improve anti-cancer cellular immune responses. Front Immunol. 2019;10:8. doi:10.3389/fimmu.2019.00008
  • Freeman-Keller M, Goldman J, Gray J. Vaccine immunotherapy in lung cancer: clinical experience and future directions. Pharmacol Ther. 2015;153:1–9. doi:10.1016/j.pharmthera.2015.05.004
  • Maarof NNN, Abdulmalek E, Fakurazi S, Rahman MBA. Biodegradable carbonate apatite nanoparticle as a delivery system to promote afatinib delivery for non-small cell lung cancer treatment. Pharmaceutics. 2022;14(6):1230. doi:10.3390/pharmaceutics14061230
  • Saleh T, Shojaosadati SA. Multifunctional nanoparticles for cancer immunotherapy. Hum Vaccin Immunother. 2016;12(7):1863–1875. doi:10.1080/21645515.2016.1147635
  • Knight FC, Gilchuk P, Kumar A, et al. Mucosal Immunization with a pH-responsive nanoparticle vaccine induces protective CD8(+) lung-resident memory T cells. ACS Nano. 2019;13(10):10939–10960. doi:10.1021/acsnano.9b00326
  • Ding B, Zheng P, Jiang F, et al. MnO(x) nanospikes as nanoadjuvants and immunogenic cell death drugs with enhanced antitumor immunity and antimetastatic effect. Angewan Chem. 2020;59(38):16381–16384. doi:10.1002/anie.202005111
  • Zhang L, Huang J, Chen X, et al. Self-assembly nanovaccine containing TLR7/8 agonist and STAT3 inhibitor enhances tumor immunotherapy by augmenting tumor-specific immune response. Journal for Immunotherapy of Cancer. 2021;9(8):e003132. doi:10.1136/jitc-2021-003132
  • An M, Liu H. Dissolving microneedle arrays for transdermal delivery of amphiphilic vaccines. Small. 2017;13(26). doi:10.1002/smll.201700164
  • Wang S, Gao J, Wang Z. Outer membrane vesicles for vaccination and targeted drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2019;11(2):e1523. doi:10.1002/wnan.1523
  • Shin MD, Shukla S, Chung YH, et al. COVID-19 vaccine development and a potential nanomaterial path forward. Nature Nanotechnol. 2020;15(8):646–655. doi:10.1038/s41565-020-0737-y
  • Hussain A, Yang H, Zhang M, et al. mRNA vaccines for COVID-19 and diverse diseases. J Control Release. 2022;345:314–333.
  • Tenchov R, Bird R, Curtze AE, Zhou Q. Lipid nanoparticles─from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano. 2021;15(11):16982–17015. doi:10.1021/acsnano.1c04996
  • Yin Y, Su W, Zhang J, et al. Separable microneedle patch to protect and deliver DNA nanovaccines against COVID-19. ACS Nano. 2021;15(9):14347–14359. doi:10.1021/acsnano.1c03252
  • Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov. 2018;17(4):261–279. doi:10.1038/nrd.2017.243
  • Smith TRF, Patel A, Ramos S, et al. Immunogenicity of a DNA vaccine candidate for COVID-19. Nat Commun. 2020;11(1):2601. doi:10.1038/s41467-020-16505-0
  • Taina-González L, de la Fuente M. The potential of nanomedicine to unlock the limitless applications of mRNA. Pharmaceutics. 2022;14(2):460. doi:10.3390/pharmaceutics14020460
  • Siva S, Hardcastle N, Kron T, et al. Ventilation/perfusion positron emission tomography--based assessment of radiation injury to lung. Int J Radiat Oncol Biol Phys. 2015;93(2):408–417. doi:10.1016/j.ijrobp.2015.06.005
  • Wu L, Wen X, Wang X, et al. Local intratracheal delivery of perfluorocarbon nanoparticles to lung cancer demonstrated with magnetic resonance multimodal imaging. Theranostics. 2018;8(2):563–574. doi:10.7150/thno.21466
  • Chow EK, Ho D. Cancer nanomedicine: from drug delivery to imaging. Sci Transl Med. 2013;5(216):216rv214. doi:10.1126/scitranslmed.3005872
  • Aghebati-Maleki A, Dolati S, Ahmadi M, et al. Nanoparticles and cancer therapy: perspectives for application of nanoparticles in the treatment of cancers. J Cell Physiol. 2020;235(3):1962–1972. doi:10.1002/jcp.29126
  • Han Z, Tu X, Qiao L, et al. Phototherapy and multimodal imaging of cancers based on perfluorocarbon nanomaterials. J Mater Chem B. 2021;9(34):6751–6769. doi:10.1039/D1TB00554E
  • Xu X, Zhang R, Liu F, et al. (19)F MRI in orthotopic cancer model via intratracheal administration of α(ν)β(3)-targeted perfluorocarbon nanoparticles. Nanomed. 2018;13(20):2551–2562. doi:10.2217/nnm-2018-0051
  • Al Faraj A, Shaik AS, Afzal S, Al Sayed B, Halwani R. MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles. Int J Nanomed. 2014;9:1491–1503. doi:10.2147/IJN.S59394
  • Tay ZW, Chandrasekharan P, Zhou XY, Yu E, Zheng B, Conolly S. In vivo tracking and quantification of inhaled aerosol using magnetic particle imaging towards inhaled therapeutic monitoring. Theranostics. 2018;8(13):3676–3687. doi:10.7150/thno.26608
  • Schmieder AH, Caruthers SD, Keupp J, Wickline SA, Lanza GM. Recent Advances in (19) fluorine magnetic resonance imaging with perfluorocarbon emulsions. Engineering (Beijing). 2015;1(4):475–489. doi:10.15302/J-ENG-2015103
  • Himmelreich U, Weber R, Ramos-Cabrer P, et al. Improved stem cell MR detectability in animal models by modification of the inhalation gas. Mol Imaging. 2005;4(2):104–109. doi:10.1162/15353500200504196
  • Rebuzzi SE, Zullo L, Rossi G, et al. Novel emerging molecular targets in non-small cell lung cancer. Int J Mol Sci. 2021;22(5). doi:10.3390/ijms22052625
  • Wu L, Liu F, Liu S, Xu X, Liu Z, Sun X. Perfluorocarbons-Based (19)F magnetic resonance imaging in biomedicine. Int J Nanomed. 2020;15:7377–7395. doi:10.2147/IJN.S255084
  • Mizuno T, Mohri K, Nasu S, Danjo K, Okamoto H. Dual imaging of pulmonary delivery and gene expression of dry powder inhalant by fluorescence and bioluminescence. J Control Release. 2009;134(2):149–154. doi:10.1016/j.jconrel.2008.11.018
  • R A, Han Z, Wang T, Zhu M, Zhou M, Sun X. Pulmonary delivery of nano-particles for lung cancer diagnosis and therapy: recent advances and future prospects. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2023;e1933. doi:10.1002/wnan.1933
  • Xu Y, Xiang J, Zhao H, et al. Human amniotic fluid stem cells labeled with up-conversion nanoparticles for imaging-monitored repairing of acute lung injury. Biomaterials. 2016;100:91–100. doi:10.1016/j.biomaterials.2016.05.034
  • Xie X, Zhan C, Wang J, Zeng F, Wu S. An activatable nano-prodrug for treating tyrosine-kinase-inhibitor-resistant non-small cell lung cancer and for optoacoustic and fluorescent imaging. Small. 2020;16(38):e2003451. doi:10.1002/smll.202003451