---
title: "Precision Nanomedicine for Pulmonary Diseases: Nanoparticle Design to Clinical Translation"
id: "pubmed-42675037"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42675037"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42675037/"
doi: "10.1038/s41392-026-02982-0"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Precision Nanomedicine for Pulmonary Diseases: Nanoparticle Design to Clinical Translation
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42675037
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42675037/)
- **DOI:** [10.1038/s41392-026-02982-0](https://doi.org/10.1038%2Fs41392-026-02982-0)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The lung is a major interface with the environment and is susceptible to environmental, infectious, and genetic insults, creating a need for improved therapies. - **Precision nanomedicine** aims to overcome limitations of conventional gene and drug therapies, including viral vector safety, therapeutic instability, poor cellular uptake, and lack of tissue- and cell-specific targeting. - **Nanoparticle-based delivery platforms** can improve therapeutic stability, bioavailability, controlled release, cellular uptake, endosomal escape, and targeted delivery to lung compartments. - The review bridges **nanoparticle bioengineering** fundamentals with a broad range of pulmonary pathologies rather than focusing on single particle types or isolated diseases. - Key nanoparticle physicochemical properties relevant to pulmonary applications are reviewed, along with advanced strategies for **targeted delivery**. - The unique lung architecture and physiology shape delivery choices; the review compares pulmonary (local) versus systemic administration, noting advantages and limitations of each route. - Applications across many diseases are examined: pulmonary fibrosis, COPD, infections, pulmonary vascular disease, cystic fibrosis, asthma, lung cancers, and neonatal pulmonary disorders. - Translational barriers discussed include biological barriers, long-term safety concerns, manufacturing challenges, and the current state of clinical trials. - The authors propose future perspectives and interdisciplinary strategies to accelerate clinical translation of nanocarriers for respiratory diseases. - The review is a comprehensive synthesis intended to inform design and translation of pulmonary **nanocarriers** while highlighting context-specific delivery strategies and unresolved translational challenges.
## Clinical Analysis & Structured Key Points
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Precision nanomedicine for pulmonary diseases: from molecular targeting to clinical translation [Zicheng Deng](https://pubmed.ncbi.nlm.nih.gov/?term=Deng+Z&cauthor_id=42675037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-1 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. dengz1@arizona.edu."), [Wen Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+W&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Jonathan Do](https://pubmed.ncbi.nlm.nih.gov/?term=Do+J&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Shravya Aragam](https://pubmed.ncbi.nlm.nih.gov/?term=Aragam+S&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Orshina Dawd](https://pubmed.ncbi.nlm.nih.gov/?term=Dawd+O&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Meghana Belthur](https://pubmed.ncbi.nlm.nih.gov/?term=Belthur+M&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Donglu Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+D&cauthor_id=42675037)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-3 "The Materials Science and Engineering Program, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-4 "Department of Biomedical Engineering, College of Engineering and Applied Science, University of Cincinnati, University of Cincinnati, Cincinnati, OH, USA."), [Tanya V Kalin](https://pubmed.ncbi.nlm.nih.gov/?term=Kalin+TV&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-5 "Phoenix Children's Center for Cancer and Blood Disorders, Phoenix, AZ, USA."), [Vladimir V Kalinichenko](https://pubmed.ncbi.nlm.nih.gov/?term=Kalinichenko+VV&cauthor_id=42675037)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-6 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. vkalin@arizona.edu.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#full-view-affiliation-7 "Division of Neonatology, Phoenix Children's Hospital, Phoenix, AZ, USA. vkalin@arizona.edu.") Affiliations Expand ### Affiliations * 1 Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. dengz1@arizona.edu. * 2 Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. * 3 The Materials Science and Engineering Program, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, USA. * 4 Department of Biomedical Engineering, College of Engineering and Applied Science, University of Cincinnati, University of Cincinnati, Cincinnati, OH, USA. * 5 Phoenix Children's Center for Cancer and Blood Disorders, Phoenix, AZ, USA. * 6 Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. vkalin@arizona.edu. * 7 Division of Neonatology, Phoenix Children's Hospital, Phoenix, AZ, USA. vkalin@arizona.edu. * PMID: **42675037** * DOI: [ 10.1038/s41392-026-02982-0 ](https://doi.org/10.1038/s41392-026-02982-0) Item in Clipboard Review # Precision nanomedicine for pulmonary diseases: from molecular targeting to clinical translation Zicheng Deng et al. Signal Transduct Target Ther. 2026. Show details Display options Display options Format Abstract PubMed PMID Signal Transduct Target Ther Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Signal+Transduct+Target+Ther%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Signal+Transduct+Target+Ther%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675037/) . 2026 Sep 1;11(1):358. doi: 10.1038/s41392-026-02982-0. ### Authors [Zicheng Deng](https://pubmed.ncbi.nlm.nih.gov/?term=Deng+Z&cauthor_id=42675037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-1 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. dengz1@arizona.edu."), [Wen Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+W&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Jonathan Do](https://pubmed.ncbi.nlm.nih.gov/?term=Do+J&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Shravya Aragam](https://pubmed.ncbi.nlm.nih.gov/?term=Aragam+S&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Orshina Dawd](https://pubmed.ncbi.nlm.nih.gov/?term=Dawd+O&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Meghana Belthur](https://pubmed.ncbi.nlm.nih.gov/?term=Belthur+M&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA."), [Donglu Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+D&cauthor_id=42675037)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-3 "The Materials Science and Engineering Program, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-4 "Department of Biomedical Engineering, College of Engineering and Applied Science, University of Cincinnati, University of Cincinnati, Cincinnati, OH, USA."), [Tanya V Kalin](https://pubmed.ncbi.nlm.nih.gov/?term=Kalin+TV&cauthor_id=42675037)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-2 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-5 "Phoenix Children's Center for Cancer and Blood Disorders, Phoenix, AZ, USA."), [Vladimir V Kalinichenko](https://pubmed.ncbi.nlm.nih.gov/?term=Kalinichenko+VV&cauthor_id=42675037)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-6 "Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. vkalin@arizona.edu.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42675037/#short-view-affiliation-7 "Division of Neonatology, Phoenix Children's Hospital, Phoenix, AZ, USA. vkalin@arizona.edu.") ### Affiliations * 1 Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. dengz1@arizona.edu. * 2 Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. * 3 The Materials Science and Engineering Program, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, USA. * 4 Department of Biomedical Engineering, College of Engineering and Applied Science, University of Cincinnati, University of Cincinnati, Cincinnati, OH, USA. * 5 Phoenix Children's Center for Cancer and Blood Disorders, Phoenix, AZ, USA. * 6 Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. vkalin@arizona.edu. * 7 Division of Neonatology, Phoenix Children's Hospital, Phoenix, AZ, USA. vkalin@arizona.edu. * PMID: **42675037** * DOI: [ 10.1038/s41392-026-02982-0 ](https://doi.org/10.1038/s41392-026-02982-0) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract The pulmonary system is a vital interface between the body and the external environment, making it highly vulnerable to environmental, infectious, and genetic insults. Precision nanomedicine offers a promising strategy to overcome the limitations of conventional gene and drug therapies, including safety concerns associated with viral vectors, instability of therapeutic agents, suboptimal cellular internalization, and a critical lack of tissue- and cell-specific targeting. Nanoparticle-based delivery platforms address these challenges by enhancing therapeutic stability and bioavailability, enabling controlled release, facilitating cellular uptake and endosomal escape, and achieving targeted delivery to specific lung compartments. While recent literature often focuses on specific nanoparticle types or isolated pathologies, this work provides a comprehensive overview of the current state of respiratory nanomedicine, bridging fundamental nanoparticle bioengineering with a wide range of pulmonary pathologies and the obstacles to clinical translation. We discuss the key physicochemical properties of nanoparticles for pulmonary biomedical applications, along with advanced design strategies for targeted delivery. Given the unique architecture and physiology of the lung, we compare the advantages and limitations of pulmonary versus systemic administration routes, emphasizing context-specific delivery strategies. Nanoparticle design and therapeutic applications are explored across a broad spectrum of diseases, including pulmonary fibrosis, chronic obstructive pulmonary disease, infections, pulmonary vascular disease, cystic fibrosis, asthma, lung cancers, and neonatal pulmonary disorders. Finally, we evaluate the current status of clinical trials, highlighting translational challenges such as biological barriers, long-term safety, and manufacturing. Future perspectives and interdisciplinary strategies are proposed to advance the clinical translation of nanocarriers for respiratory diseases. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Competing interests: The authors declare no competing interests. ## References 1. 1. Sikkema, L. et al. An integrated cell atlas of the lung in health and disease. Nat. Med. 29, 1563–1577 (2023). - [DOI](https://doi.org/10.1038/s41591-023-02327-2) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/37291214/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10287567/) 2. 1. Wang, C. C. et al. Airborne transmission of respiratory viruses. Science 373, eabd9149 (2021). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34446582/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8721651/) - [DOI](https://doi.org/10.1126/science.abd9149) 3. 1. Mitchell, M. J. et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20, 101–124 (2021). - [DOI](https://doi.org/10.1038/s41573-020-0090-8) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/33277608/) 4. 1. Bulcha, J. T. et al. Viral vector platforms within the gene therapy landscape. Signal Transduct. Target Ther. 6, 53 (2021). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/33558455/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/7868676/) - [DOI](https://doi.org/10.1038/s41392-021-00487-6) 5. 1. Lundstrom, K. Viral vectors in gene therapy: where do we stand in 2023? Viruses 15, 698 (2023). - [PubMed](https://pubmed.ncbi.nlm.nih.gov/36992407/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10059137/) - [DOI](https://doi.org/10.3390/v15030698) Show all 495 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675037/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42675037/) * Drug Delivery Systems* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Drug+Delivery+Systems%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Drug+Delivery+Sy
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