Organism‐Generated Biological Vesicles In Situ: An Emerging Drug Delivery Strategy

Kong, Li; Yang, Conglian; Zhang, Zhiping

doi:10.1002/advs.202204178

Cited by 9 publications

(5 citation statements)

References 127 publications

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“…Reduction of renal blood flow is considered to be one of important pathogenic steps in the development of AKI, which usually results in decreased kidney perfusion. If reduced renal blood flow is reversed rapidly, the kidney is less prone to injury, including structural (acute tubular necrosis) and functional (proteinuria) damages 50 - 52 . Here, we report that the renal tubule specific knockout of ELA reduces renal blood flow and aggravates tubular injury (Figure 4 ) under the injury, while administration of ELA peptide increases renal blood flow and relieves tubular damage (Figure 8 ).…”

Section: Discussionmentioning

confidence: 99%

Tubular Elabela-APJ axis attenuates ischemia-reperfusion induced acute kidney injury and the following AKI-CKD transition by protecting renal microcirculation

Xiong¹,

Hong²,

Yang³

et al. 2023

Theranostics

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Rationale: Ischemia-reperfusion injury (I/R) is a common cause of acute kidney injury (AKI). Post-ischemic recovery of renal blood supply plays an important role in attenuating injury. Exogenous application of elabela (ELA) peptides has been demonstrated by us and others to alleviate AKI, partly through its receptor APJ. However, the endogenous role of ELA in renal I/R remains unclear. Methods: Renal tubule specific ELA knockout (Apela Ksp KO) mice challenged with bilateral or unilateral I/R were used to investigate the role of endogenous ELA in renal I/R. RNA-sequencing analysis was performed to unbiasedly investigate altered genes in kidneys of Apela Ksp KO mice. Injured mice were treated with ELA32 peptide, Nω-hydroxy-nor-L-arginine (nor-NOHA), prostaglandin E2 (PGE2), Paricalcitol, ML221 or respective vehicles, individually or in combination. Results: ELA is mostly expressed in renal tubules. Aggravated pathological injury and further reduction of renal microvascular blood flow were observed in Apela Ksp KO mice during AKI and the following transition to chronic kidney disease (AKI-CKD). RNA-seq analysis suggested that two blood flow regulators, arginine metabolizing enzyme arginase 2 (ARG2) and PGE2 metabolizing enzyme carbonyl reductases 1 and 3 (CBR1/3), were altered in injured Apela Ksp KO mice. Notably, combination application of an ARG2 inhibitor nor-NOHA, and Paricalcitol, a clinically used activator for PGE2 synthesis, alleviated injury-induced AKI/AKI-CKD stages and eliminated the worst outcomes observed in Apela Ksp KO mice. Moreover, while the APJ inhibitor ML221 blocked the beneficial effects of ELA32 peptide on AKI, it showed no effect on combination treatment of nor-NOHA and Paricalcitol. Conclusions: An endogenous tubular ELA-APJ axis regulates renal microvascular blood flow that plays a pivotal role in I/R-induced AKI. Furthermore, improving renal blood flow by inhibiting ARG2 and activating PGE2 is an effective treatment for AKI and prevents the subsequent AKI-CKD transition.

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Section: Discussionmentioning

confidence: 99%

Tubular Elabela-APJ axis attenuates ischemia-reperfusion induced acute kidney injury and the following AKI-CKD transition by protecting renal microcirculation

Xiong¹,

Hong²,

Yang³

et al. 2023

Theranostics

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“…(5) The risk of altering the orientation of membrane proteins when performing membrane-disrupting manipulations such as drug delivery to exosomes, which may result in recognition by the immune system and subsequent adverse reactions. Recently, in situ exosome-based drug delivery strategies based on organism generation have provided researchers with a new idea, which involves transforming in vitro isolation, drug loading, and modified delivery into in situ release at the lesion site, thus avoiding the risk of altering exosome properties and characteristics [ 222 ]. (6) Criteria for manufacturing, loading efficiency, purification, storage, use, stability duration, dose, and application are yet to be determined [ 223 ].…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

Yang,

Li,

et al. 2024

J Nanobiotechnol

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Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although the current tumor treatment methods have therapeutic effect to a certain extent, they still have some shortcomings such as poor water solubility, short half-life, local and systemic toxicity. Therefore, how to deliver therapeutic agent so as to realize safe and effective anti-tumor therapy become a problem urgently to be solved in this field. As a medium of information exchange and material transport between cells, exosomes are considered to be a promising drug delivery carrier due to their nano-size, good biocompatibility, natural targeting, and easy modification. In this review, we summarize recent advances in the isolation, identification, drug loading, and modification of exosomes as drug carriers for tumor therapy alongside their application in tumor therapy. Basic knowledge of exosomes, such as their biogenesis, sources, and characterization methods, is also introduced herein. In addition, challenges related to the use of exosomes as drug delivery vehicles are discussed, along with future trends. This review provides a scientific basis for the application of exosome delivery systems in oncological therapy. Graphical Abstract

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“…For instance, it has been shown that due to the presence of CD47 on the surface of exosomes, phagocytosis by circulating monocytes can be efficiently avoided, thus promoting the metastasis of cargo. Therefore, using exosomes as carriers and modifying them for clinical applications by artificially optimizing the integration of specific loads such as tumor drugs and targeted siR-NAs is a promising and inspiring idea [99,100]. This denotes that exosome-based therapies are emerging cutting-edge strategies to inhibit tumor progression.…”

Section: Macrophage-derived Exosomes For Cancer Therapymentioning

confidence: 99%

"Macrophage-Derived Exosomes in Tumor Progression and as Promising Tools for Cancer Therapy"

2023

BJSTR

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Tumor progression is one of the major challenges in cancer treatment, and macrophages, as an important component of the immune system, have been extensively studied for their role in tumor immunomodulation. Exosomes are a group of small vesicles secreted by cells containing a variety of biologically active molecules, such as proteins, nucleic acids, and lipids. Recent studies have shown that exosomes serve as an important messenger for macrophages, which participate in the regulation of tumor growth, metastasis, immune escape and drug resistance by releasing exosomes. In addition, macrophage-derived exosomes play an influential role in tumor immunotherapy. They can transport immunomodulatory molecules, such as cytokines and antigens, which interact with tumor cells and other immune cells to facilitate immune recognition and killing of tumors. Macrophage-derived exosomes also modulate tumor-induced immunosuppression and enhance anti-tumor immune response. Consequently, the role of macrophage-derived exosomes in tumors may be dual, with both antitumor and tumorpromoting effects. A better understanding of macrophage-derived exosomes will provide new strategies to improve the efficacy of anticancer therapies. In this review, we focus on the biogenesis of macrophagederived exosomes and the mechanisms by which they mediate cancer progression, including on tumor cell proliferation, angiogenesis, invasion and metastasis, immune evasion and drug resistance. Finally, we discuss the potential clinical application of macrophage-derived exosomes as a promising strategy for tumor immunotherapy, hoping to provide new ideas and targets for further exploration of tumor pathogenesis and therapeutic approaches.

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Organism‐Generated Biological Vesicles In Situ: An Emerging Drug Delivery Strategy

Cited by 9 publications

References 127 publications

Tubular Elabela-APJ axis attenuates ischemia-reperfusion induced acute kidney injury and the following AKI-CKD transition by protecting renal microcirculation

Tubular Elabela-APJ axis attenuates ischemia-reperfusion induced acute kidney injury and the following AKI-CKD transition by protecting renal microcirculation

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

"Macrophage-Derived Exosomes in Tumor Progression and as Promising Tools for Cancer Therapy"

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