Advances in nanomaterial-targeted treatment of acute lung injury after burns

Abstract

Acute lung injury (ALI) is a common complication in patients with severe burns and has a complex pathogenesis and high morbidity and mortality rates. A variety of drugs have been identified in the clinic for the treatment of ALI, but they have toxic side effects caused by easy degradation in the body and distribution throughout the body. In recent years, as the understanding of the mechanism underlying ALI has improved, scholars have developed a variety of new nanomaterials that can be safely and effectively targeted for the treatment of ALI. Most of these methods involve nanomaterials such as lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles and other nanomaterials, which are targeted to reach lung tissues to perform their functions through active targeting or passive targeting, a process that involves a variety of cells or organelles. In this review, first, the mechanisms and pathophysiological features of ALI occurrence after burn injury are reviewed, potential therapeutic targets for ALI are summarized, existing nanomaterials for the targeted treatment of ALI are classified, and possible problems and challenges of nanomaterials in the targeted treatment of ALI are discussed to provide a reference for the development of nanomaterials for the targeted treatment of ALI.

Keywords: ALI; Burn; Camouflaged nanoparticles; Nanomaterials; Targeted treatment.

Fig. 1

Schematic strategy for the nanomaterial-targeted treatment of ALI.

Fig. 2

Mechanisms and changes in the internal environment of ALI after burn injury

Fig. 3

Progress in the occurrence of ALI. (A) The normal alveolar–capillary membrane is a barrier that prevents the development of alveolar edema. With the progression from mild (B) to severe injury (C), the alveolar–capillary barrier becomes more permeable, leading to alveolar edema. adapted with permission from ref [40].,copyright 2022, Elsevier

Fig. 4

Passive lung targeting of CS-PBA-Cro microspheres after intravenous injection. (A) Representative fluorescence images and (B) quantitative analysis of label-free or Cy5.5-labeled CS microspheres in the main tissues at different time intervals after intravenous injection (1 min, 6 h, 24 h and 48 h). (C) Distribution of label-free or Cy5.5-labeled CS microspheres in cryosections of lungs after intravenous injection. (D) Graphical abstract. adapted with permission from ref [64]., Copyright 2023, Elsevier

Fig. 5

FITC-Esbp-BSANPs can target the lungs in an established ALI mouse model, and the nanoparticles are distributed in vivo. (A) TEM image; (B) UV images of the hydrolysate of Fitc, Fitc-labeled Esbp, DXM-loaded BSANP hydrolysate, and DXM-loaded Fitc-Esbp-BSANP hydrolysate from 200 to 600 nm. H&E staining of lung sections (C) of mice (in the normal group and inflammatory group) and in vivo organ images (D) from left to right: heart, liver, spleen, lung, and kidney) of mice in the inflammatory group. adapted with permission from ref [70].,copyright 2019, SPRINGER.

Fig. 6

Inhalation of MPS/D-SEL promoted dysregulated NET degradation in ALI mice. (A) Illustration of the MPS/D-SEL construction. (B) MPS/D-SELs displayed superior mucus penetration ability and were retained in the alveoli after inhalation. DNase I was then released from the nanocarrier first after responding to MMP-9, resulting in inner SEL core exposure, which precisely delivered MPS into macrophages to promote M2 macrophage polarization. (C) The synergistic anti-inflammatory effects of MPS/D-SEL include the degradation of dysregulated NETs, suppression of the mucus-blocking microenvironment, and promotion of M2 macrophage polarization. Adapted with permission from ref [88].,copyright 2023, American Chemical Society

Fig. 7

NPs/miR-223 switches the M1 phenotype to the M2 phenotypein vitro. Schematic representation of the design, synthesis, and delivery of NPs/miR-223 for sepsis treatment. Mechanistically, NPs/miR-223 switched M1 macrophages to the M2 phenotype by targeting Pknox1 and inhibiting the activation of the NF-κB signaling pathway. adapted with permission from ref [108].,Copyright 2023, Wiley-VCH.

Fig. 8

Exploration of the mechanism of mitophagy promotion by the single-atom catalyst Pt/CeO2. (A) Synthesis process of single-atom catalysts (SACs) Pt/CeO2. (B) Extraction and activation of neutrophil-like (HL-60) cell membranes, modification of the rabies virus glycoprotein (RVG29) peptide on HL-60 cell membranes, and preparation of SACs with a core − shell structure. (C)In vivo mechanism of action of core − shell-structured SACs. adapted with permission from ref [113].,copyright 2023, the American Chemical Society

Fig. 9

Effect of cDC manipulation on lung edema and lung injury. (A) Hematoxylin and eosin staining (magnification, ×200) of lung tissues at 6 h and (B) at 24 h post-LPS challenge. (C) Lung injury score at 6 h and (D) at 24 h post-LPS challenge. (E) LWW/BW at 6 h and (F) at 24 h post-LPS challenge. The lung injury score is expressed as an arbitrary mean. The data are presented as the mean ± standard deviation (n = 6). adapted with permission from ref [120].,copyright 2019, Spandidos

Fig. 10

Design and characterization of LET-EVs-miRNA-125b. (A) Schematic diagram of the preparation of LET-EVs-miRNA125b. (B) Schematic of the construction and production of the LAMP-2B-LET fusion protein plasmid. (C) Size distribution and particle distribution of EVs and LET-EVs, as measured via NTA. (D) The morphology of EVs and LET-EVs was a typical cup-shaped structure, as detected by TEM. (E) EV-positive (LAMP-2B, CD63, CD81, and TSG101) and -negative (calnexin) markers were detected in LAMP-2B-EVs, LAMP-2B-LET-EVs, and their donor cells by western blotting. (F) The loading efficiency of miRNA-125b-5p was detected using qRT‒PCR to compare the relative expression of miRNA-125b-5p between LET-EVs and LET-EVs-miRNA-125b (n = 3). adapted with permission from ref [158].,Copyright 2023, Wiley-VCH