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<p>Chronic obstructive pulmonary disease (COPD) and acute lung injury (ALI) are among the leading causes of respiratory morbidity and mortality worldwide, imposing a substantial healthcare burden. Current therapeutic approaches primarily focus on symptomatic relief and often fail to adequately address persistent inflammation, oxidative stress, and inefficient drug delivery to diseased lung tissues. In this context, metal-organic frameworks (MOFs) have emerged as promising drug delivery platforms owing to their high surface area, tunable porosity, and versatile structural properties. These features enable the efficient encapsulation and controlled release of anti-inflammatory agents, antioxidants, nucleic acids, and biologics at targeted pulmonary sites. This review summarizes recent advances in inhalable MOF-based systems for the treatment of pulmonary disorders, with particular emphasis on COPD and inflammatory lung injury. Key design considerations, including the selection of biocompatible metal nodes and organic linkers, optimization of aerodynamic properties for inhalation, and development of biodegradable and stable frameworks, are discussed. Furthermore, various synthesis strategies, including solvothermal, microwave-assisted, mechanochemical, electrochemical, and sonochemical methods, are examined for their roles in tailoring MOF structure and functionality. The therapeutic mechanisms of MOFs are highlighted, including modulation of neutrophilic inflammation, suppression of pro-inflammatory cytokines, regulation of nuclear factor-kappa B (NF-κB) signaling pathways, and mitigation of oxidative stress through catalytic antioxidant activity. In addition, the review addresses critical translational challenges, such as pulmonary biological barriers, biosafety concerns, scalable manufacturing, and regulatory considerations. Looking ahead, advances in stimuli-responsive, multifunctional, and precision-engineered MOFs are expected to accelerate the development of next-generation pulmonary therapeutics and facilitate their transition from preclinical research to clinical application.</p> Graphical Abstract <p></p>

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Design principles and mechanisms of metal organic frameworks establish them as advanced pulmonary therapeutics with broad translational opportunities

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月4日

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  • Sakshi C. Wankhede,
  • Rahul G. Ingle,
  • Anil M. Pethe

摘要

Chronic obstructive pulmonary disease (COPD) and acute lung injury (ALI) are among the leading causes of respiratory morbidity and mortality worldwide, imposing a substantial healthcare burden. Current therapeutic approaches primarily focus on symptomatic relief and often fail to adequately address persistent inflammation, oxidative stress, and inefficient drug delivery to diseased lung tissues. In this context, metal-organic frameworks (MOFs) have emerged as promising drug delivery platforms owing to their high surface area, tunable porosity, and versatile structural properties. These features enable the efficient encapsulation and controlled release of anti-inflammatory agents, antioxidants, nucleic acids, and biologics at targeted pulmonary sites. This review summarizes recent advances in inhalable MOF-based systems for the treatment of pulmonary disorders, with particular emphasis on COPD and inflammatory lung injury. Key design considerations, including the selection of biocompatible metal nodes and organic linkers, optimization of aerodynamic properties for inhalation, and development of biodegradable and stable frameworks, are discussed. Furthermore, various synthesis strategies, including solvothermal, microwave-assisted, mechanochemical, electrochemical, and sonochemical methods, are examined for their roles in tailoring MOF structure and functionality. The therapeutic mechanisms of MOFs are highlighted, including modulation of neutrophilic inflammation, suppression of pro-inflammatory cytokines, regulation of nuclear factor-kappa B (NF-κB) signaling pathways, and mitigation of oxidative stress through catalytic antioxidant activity. In addition, the review addresses critical translational challenges, such as pulmonary biological barriers, biosafety concerns, scalable manufacturing, and regulatory considerations. Looking ahead, advances in stimuli-responsive, multifunctional, and precision-engineered MOFs are expected to accelerate the development of next-generation pulmonary therapeutics and facilitate their transition from preclinical research to clinical application.

Graphical Abstract