ABSTRACT
Injudicious or inappropriate use of antibiotics has led to the prevalence of drug-resistant bacteria, posing a huge menace to global health. Here, a self-assembled aggregation-induced emission (AIE) nanosphere (AIE-PEG1000 NPs) that simultaneously possesses near-infrared region II (NIR-II) fluorescence emissive, photothermal, and photodynamic properties is prepared using a multifunctional AIE luminogen (AIE-4COOH). The AIE-PEG1000 NPs were encapsulated with teicoplanin (Tei) and ammonium bicarbonate (AB) into lipid nanovesicles to form a laser-activated "nanobomb" (AIE-Tei@AB NVs) for the multimodal theranostics of drug-resistant bacterial infections. In vivo experiments validate that the "nanobomb" enables high-performance NIR-II fluorescence, infrared thermal, and ultrasound (AB decomposition during the photothermal process to produce numerous CO2/NH3 bubbles, which is an efficient ultrasound contrast agent) imaging of multidrug-resistant bacteria-infected foci after intravenous administration of AIE-Tei@AB NVs followed by 660 nm laser stimulation. The highly efficient photothermal and photodynamic features of AIE-Tei@AB NVs, combined with the excellent pharmacological property of rapidly released Tei during bubble generation and NV disintegration, collectively promote broad-spectrum eradication of three clinically isolated multidrug-resistant bacteria strains and rapid healing of infected wounds. This multimodal imaging-guided synergistic therapeutic strategy can be extended for the theranostics of superbugs.
Subject(s)
Bacterial Infections , Nanoparticles , Nanospheres , Photochemotherapy , Humans , Light , Diagnostic Imaging , Bacterial Infections/diagnostic imaging , Bacterial Infections/drug therapy , Theranostic Nanomedicine/methods , Nanoparticles/therapeutic useABSTRACT
Chronic wound healing remains a challenging medical problem affecting society, which urgently requires anatomical and functional solutions. Adipose-derived stem cells (ADSCs), mesenchymal stem cells with self-renewal and multiple differentiation ability, play essential roles in wound healing and tissue regeneration. The exosomes from ADSCs (ADSC-EXOs) are extracellular vesicles that are essential for communication between cells. ADSC-EXOs release various bioactive molecules and subsequently restore tissue homeostasis and accelerate wound healing, by promoting various stages of wound repair, including regulating the inflammatory response, promoting wound angiogenesis, accelerating cell proliferation, and modulating wound remodeling. Compared with ADSCs, ADSC-EXOs have the advantages of avoiding ethical issues, being easily stored, and having high stability. In this review, a literature search of PubMed, Medline, and Google Scholar was performed for articles before August 1, 2022 focusing on exosomes from ADSCs, chronic wound repair, and therapeutic potential. This review aimed to provide new therapeutic strategies to help investigators explore how ADSC-EXOs regulate intercellular communication in chronic wounds.
ABSTRACT
Burn injury is an intractable problem in the field of surgery where screening relevant target genes and exploring pathological mechanisms through bioinformatic methods has become a necessity. Herein, we integrated three burn injury mRNA microarray datasets from the Gene Expression Omnibus database to analyze the hub differentially expressed genes (DEGs) between burn injury patient samples and healthy human samples; we conducted multiple functional enrichment analyses and constructed the protein-protein interaction (PPI) network. Finally, we evaluated the immune infiltration in the burn injury microenvironment. A total of 84 intersection DEGs (32 upregulated and 52 downregulated) were screened in burn injury patients via integrated analyses. Upregulated genes were primarily enriched in regulation of T cell activation, regulation of response to DNA damage stimulus, positive regulation of innate immune response, positive regulation of defense response. We also identified 10 hub genes from the PPI network (CCNB2, MYO10, TTK, POLQ, VASP, TIMP1, CDK16, MMP1, ZYX, and PKMYT1). Next, we found that 22 immune cells were substantially changed during the burn injury by CIBERSORT. In addition, we verified that VASP and POLQ are two novel diagnostic markers in burn processes with high diagnostic efficacy via immunohistochemistry. In summary, we identified several key genes involved in burn injury and provided a favorable basis for elucidating the molecular mechanisms of burn injury through comprehensive bioinformatic analysis.