“Find-eat” strategy targeting endothelial cells via receptor functionalized apoptotic body nanovesicle

Qian, Shutong; Mao, Jiayi; Zhao, Qing; Zhao, Binfan; Liu, Zhimo; Lu, Bolun; Zhang, Liucheng; Mao, Xiyuan; Zhang, Yuguang; Wang, Danru; Sun, Xiaoming; Cui, Wenguo

doi:10.1016/j.scib.2023.03.030

Cited by 15 publications

(8 citation statements)

References 44 publications

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“…Notably, the OD/GM/QCS@Exo group exhibited significantly lower relative TNF-α expression levels (33.3 ± 3.8%) compared to the other treatment groups (Figure E). Furthermore, angiogenesis within the wound tissue was evaluated using vascular markers CD31 and α-SMA. , Our findings demonstrated a significant increase in CD31 expression levels within the OD/GM/QCS@Exo group when compared to the blank control group (Figure C), with a corresponding relative expression of approximately 41.2 ± 3.6% (Figure F). Overall, the OD/GM/QCS@Exo hydrogel could promote healing of bacterial infected wounds through effective eradication of pathogenic bacteria from wound sites, attenuation of inflammatory responses, stimulation of angiogenesis, and acceleration of granulation tissue formation and re-epithelialization.…”

Section: Resultsmentioning

confidence: 71%

Visible-Light Cross-Linkable Multifunctional Hydrogels Loaded with Exosomes Facilitate Full-Thickness Skin Defect Wound Healing through Participating in the Entire Healing Process

Lv,

Li,

Zhang

et al. 2024

ACS Appl. Mater. Interfaces

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The management of severe full-thickness skin defect wounds remains a challenge due to their irregular shape, uncontrollable bleeding, high risk of infection, and prolonged healing period. Herein, an all-in-one OD/GM/QCS@Exo hydrogel was prepared with catecholmodified oxidized hyaluronic acid (OD), methylacrylylated gelatin (GM), and quaternized chitosan (QCS) and loaded with adipose mesenchymal stem cell-derived exosomes (Exos). Cross-linking of the hydrogel was achieved using visible light instead of ultraviolet light irradiation, providing injectability and good biocompatibility. Notably, the incorporation of catechol groups and multicross-linked networks in the hydrogels conferred strong adhesion properties and mechanical strength against external forces such as tensile and compressive stress. Furthermore, our hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties along with wound-healing promotion effects. Our results demonstrated that the hydrogel-mediated release of Exos significantly promotes cellular proliferation, migration, and angiogenesis, thereby accelerating skin structure reconstruction and functional recovery during the wound-healing process. Overall, the all-in-one OD/GM/QCS@Exo hydrogel provided a promising therapeutic strategy for the treatment of full-thickness skin defect wounds through actively participating in the entire process of wound healing.

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Section: Resultsmentioning

confidence: 71%

Visible-Light Cross-Linkable Multifunctional Hydrogels Loaded with Exosomes Facilitate Full-Thickness Skin Defect Wound Healing through Participating in the Entire Healing Process

Lv,

Li,

Zhang

et al. 2024

ACS Appl. Mater. Interfaces

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“…CX3CL1 is a chemokine that specifically binds to PS, and CX3CL1/CX3CR1 has been considered a specific receptor/ligand that mediates MSC‐ApoVs phagocytosis. [ 12 , 18 ] Therefore, we assessed CX3CL1 expression in MSCs and each group of ApoVs via western blotting. CX3CL1 was expressed in all groups but was slightly down‐regulated in Hypo‐ApoVs (Figure 2E ; Figure S2C , Supporting information).…”

Section: Resultsmentioning

confidence: 99%

“…Then, a subsequent centrifugation step was performed at 3000 g for 10 min to obtain ApoVs of the appropriate size, named Hypo‐ApoVs, Oxi‐ApoVs, or Con‐ApoVs. [ 12 , 45 ] ApoVs were washed twice with PBS and resuspended and stored at −80 °C for subsequent experiments. Protein concentrations of ApoVs were determined using the BCA protein assay kit (abs9232, Absin, Shanghai, China) following the manufacturer's guidelines.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous studies have demonstrated that nanovesicles fabricated from MSC‐AB membranes promote vascularization by biotargeting ECs for drug delivery through a “Find‐Eat” strategy. [ 12 ] However, the effects of intercellular signal molecules present in ApoV cargo on angiogenesis have not yet been fully elucidated under the specific microenvironment targeting endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Biogenerated Oxygen‐Related Environmental Stressed Apoptotic Vesicle Targets Endothelial Cells

Zhao,

Lu,

Qian

et al. 2024

Advanced Science

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The dynamic balance between hypoxia and oxidative stress constitutes the oxygen‐related microenvironment in injured tissues. Due to variability, oxygen homeostasis is usually not a therapeutic target for injured tissues. It is found that when administered intravenously, mesenchymal stem cells (MSCs) and in vitro induced apoptotic vesicles (ApoVs) exhibit similar apoptotic markers in the wound microenvironment where hypoxia and oxidative stress co‐existed, but MSCs exhibited better effects in promoting angiogenesis and wound healing. The derivation pathway of ApoVs by inducing hypoxia or oxidative stress in MSCs to simulate oxygen homeostasis in injured tissues is improved. Two types of oxygen‐related environmental stressed ApoVs are identified that directly target endothelial cells (ECs) for the accurate regulation of vascularization. Compared to normoxic and hypoxic ones, oxidatively stressed ApoVs (Oxi‐ApoVs) showed the strongest tube formation capacity. Different oxygen‐stressed ApoVs deliver similar miRNAs, which leads to the broad upregulation of EC phosphokinase activity. Finally, local delivery of Oxi‐ApoVs‐loaded hydrogel microspheres promotes wound healing. Oxi‐ApoV‐loaded microspheres achieve controlled ApoV release, targeting ECs by reducing the consumption of inflammatory cells and adapting to the proliferative phase of wound healing. Thus, the biogenerated apoptotic vesicles responding to oxygen‐related environmental stress can target ECs to promote vascularization.

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“…Recent studies have shown that chronic hypoxia in wounds leads to increased expression of CX3CR1 in ECs, resulting in impaired angiogenesis. Targeting CX3CR1 can improve damage in chronic wounds 58 . Transcriptome sequencing and analysis of differential gene expression showed significant activation of the leukocyte adhesion and rolling pathway following the coculture of LECs with NETs.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage

Zhang,

Chen,

et al. 2024

Theranostics

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Rationale: Hydrocephalus is a substantial complication after intracerebral hemorrhage (ICH) or intraventricular hemorrhage (IVH) that leads to impaired cerebrospinal fluid (CSF) circulation. Recently, brain meningeal lymphatic vessels (mLVs) were shown to serve as critical drainage pathways for CSF. Our previous studies indicated that the degradation of neutrophil extracellular traps (NETs) after ICH/IVH alleviates hydrocephalus. However, the mechanisms by which NET degradation exerts beneficial effects in hydrocephalus remain unclear. Methods: A mouse model of hydrocephalus following IVH was established by infusing autologous blood into both wildtype and Cx3cr1 -/- mice. By studying the features and processes of the model, we investigated the contribution of mLVs and NETs to the development and progression of hydrocephalus following secondary IVH. Results: This study observed the widespread presence of neutrophils, fibrin and NETs in mLVs following IVH, and the degradation of NETs alleviated hydrocephalus and brain injury. Importantly, the degradation of NETs improved CSF drainage by enhancing the recovery of lymphatic endothelial cells (LECs). Furthermore, our study showed that NETs activated the membrane protein CX3CR1 on LECs after IVH. In contrast, the repair of mLVs was promoted and the effects of hydrocephalus were ameliorated after CX3CR1 knockdown and in Cx3cr1 -/- mice. Conclusion: Our findings indicated that mLVs participate in the development of brain injury and secondary hydrocephalus after IVH and that NETs contribute to acute LEC injury and lymphatic thrombosis. CX3CR1 is a key molecule in NET-induced LEC damage and meningeal lymphatic thrombosis, which leads to mLV dysfunction and exacerbates hydrocephalus and brain injury. NETs may be a critical target for preventing the obstruction of meningeal lymphatic drainage after IVH.

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“Find-eat” strategy targeting endothelial cells via receptor functionalized apoptotic body nanovesicle

Cited by 15 publications

References 44 publications

Visible-Light Cross-Linkable Multifunctional Hydrogels Loaded with Exosomes Facilitate Full-Thickness Skin Defect Wound Healing through Participating in the Entire Healing Process

Visible-Light Cross-Linkable Multifunctional Hydrogels Loaded with Exosomes Facilitate Full-Thickness Skin Defect Wound Healing through Participating in the Entire Healing Process

Biogenerated Oxygen‐Related Environmental Stressed Apoptotic Vesicle Targets Endothelial Cells

Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage

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