2. Academic Validation
  3. Spore-inspired surface engineering enhances macrophage phagocytosis for inhalation therapy of acute lung injury

Spore-inspired surface engineering enhances macrophage phagocytosis for inhalation therapy of acute lung injury

  • J Control Release. 2026 May 10:393:114833. doi: 10.1016/j.jconrel.2026.114833.
Xi Kuang 1,  Qiaoying Jiang 2,  Ziwei Guo 1,  Hongming Cui 1,  Jiayun Guo 1,  Kejin Fang 3,  Yihao Ye 3,  Wenwei Cai 1,  Zhengwei Mao 4,  Mengqi Tong 5,  Yueliang Zheng 6
Affiliations

Affiliations

  • 1 Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China.
  • 2 School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
  • 3 Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China; The Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou 311121, China.
  • 4 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
  • 5 Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China; Translational Medicine Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China. Electronic address: [email protected].
  • 6 Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China. Electronic address: [email protected].
PMID: 41850404 DOI: 10.1016/j.jconrel.2026.114833
Abstract

Acute lung injury (ALI) is a life-threatening pulmonary disease characterized by oxidative stress and excessive inflammation. Although quercetin (QU) has strong antioxidant and anti-inflammatory activity, the effect of inhalation administration is still limited due to its insufficient deposition in the alveoli and low uptake efficiency by alveolar macrophages. To overcome these obstacles, we have developed a biomimetic inhalable platform quercetin-loaded carbonized Aspergillus oryzae spore (QU-cASP) inspired by the microstructure of Fungal spores. The carbonized Aspergillus oryzae spore (cASP) retained the native microstructure of the spores while forming a carbonaceous skeleton, thereby enhancing drug-loading capacity and structural stability. Meanwhile, its rough surface significantly enhanced the surface-assisted phagocytic effect of macrophages, thus promoting the intracellular delivery of QU. In addition, the mass median aerodynamic diameter (MMAD) of QU-cASP fell within the optimal inhalable range, enabling efficient pulmonary deposition. In the ALI models, inhalation of QU-cASP could effectively relieve oxidative stress, reduce pro-inflammatory cytokines, and promote macrophage polarization toward the anti-inflammatory M2 phenotype. Transcriptomic analysis and Western blot analysis showed that the inflammatory-related signaling pathway was inhibited. In summary, this study establishes a spore-inspired surface-assisted phagocytosis strategy, which bridges the gap between aerodynamic delivery and cell delivery. Meanwhile, QU-cASP holds a remarkable translational prospect for the precision treatment of ALI and related lung inflammatory diseases.

Keywords

Acute lung injury; Aspergillus oryzae spores; Macrophage phagocytosis; Pulmonary drug delivery; Quercetin.

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