Assessing the targeting and fate of cathepsin k antibody-modified nanoparticles in a rat abdominal aortic aneurysm model

Camardo, Andrew; Carney, Sarah; Ramamurthi, Anand

doi:10.1016/j.actbio.2020.05.037

Cited by 13 publications

(9 citation statements)

References 34 publications

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“… 290 Camardo et al previously demonstrated that cathepsin K is overexpressed in aneurysm tissue and can be used as a potential target, so they combined matrix regenerated PEG-PLGA nanoparticles with antibodies to cathepsin K for targeted therapy of aortic aneurysms. 291 MMP inhibitors have been widely studied as a potential treatment for AAA. However, due to low efficacy at low doses and high toxicity at high doses, an appropriate delivery system is urgently needed.…”

Section: Clinical Cohort Studymentioning

confidence: 99%

The mechanism and therapy of aortic aneurysms

Gao

Cao

et al. 2023

Sig Transduct Target Ther

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Aortic aneurysm is a chronic aortic disease affected by many factors. Although it is generally asymptomatic, it poses a significant threat to human life due to a high risk of rupture. Because of its strong concealment, it is difficult to diagnose the disease in the early stage. At present, there are no effective drugs for the treatment of aneurysms. Surgical intervention and endovascular treatment are the only therapies. Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm, the specific mechanisms remain unclear. Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment. To better understand aortic aneurysm, this review elaborates on the discovery history of aortic aneurysm, main classification and clinical manifestations, related molecular mechanisms, clinical cohort studies and animal models, with the ultimate goal of providing insights into the treatment of this devastating disease. The underlying problem with aneurysm disease is weakening of the aortic wall, leading to progressive dilation. If not treated in time, the aortic aneurysm eventually ruptures. An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall. The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.

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Section: Clinical Cohort Studymentioning

confidence: 99%

The mechanism and therapy of aortic aneurysms

Gao

Cao

et al. 2023

Sig Transduct Target Ther

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“…Therefore, other responsive nanoparticles designed based on the enzymatic reaction substrates of other cathepsin family members may be potentially employed for atherosclerosis treatment. In addition to atherosclerosis, CTSK is upregulated in other diseases, such as osteoporosis 58 , cancer 59 , 60 , aortic aneurysms 61 , and heart disease 62 , and CTSK responsive strategy can be used to release drugs to treat these diseases 63 , 64 .…”

Section: Discussionmentioning

confidence: 99%

Inflammatory endothelium-targeted and cathepsin responsive nanoparticles are effective against atherosclerosis

Fang

et al. 2022

Theranostics

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Rationale: Atherosclerosis is characterized by lipid accumulation, plaque formation, and artery stenosis. The pharmacological treatment is a promising therapy for atherosclerosis, but this approach faces major challenges such as targeted drug delivery, controlled release, and non-specific clearance. Methods: Based on the finding that the cathepsin k (CTSK) enzyme is enriched in atherosclerotic lesions, we constructed an integrin α v β 3 targeted and CTSK-responsive nanoparticle to control the release of rapamycin (RAP) locally. The targeted and responsive nanoparticles (T/R NPs) were engineered by the self-assembly of a targeting polymer PLGA-PEG-c(RGDfC) and a CTSK-sensitive polymer PLGA-Pep-PEG. PLGA-Pep-PEG was also modified with a pair of FRET probe to monitor the hydrolysis events. Results: Our results indicated that RAP@T/R NPs accelerated the release of RAP in response to CTSK stimulation in vitro , which significantly inhibited the phagocytosis of OxLDL and the release of cytokines by inflammatory macrophages. Additionally, T/R NPs had prolonged blood retention time and increased accumulation in the early and late stage of atherosclerosis lesions. RAP@T/R NPs significantly blocked the development of atherosclerosis and suppressed the systemic and local inflammation in ApoE -/- mice. Conclusions: RAP@T/R NPs hold a great promise as a drug delivery system for safer and more efficient therapy of atherosclerosis.

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“…A recent study analyzed the plasma activation levels of complement C3 induced by the intravenous injection of PEG-PLGA NPs conjugated with anti-cathepsin K antibodies. The results revealed no significant upregulation of complement C3 after treatment with the modified NPs, suggesting that they not induce an immune response (Camardo et al, 2020). DOX-loaded PEG-PLGA NPs decorated with biotin showed low hemolytic activity and cytotoxicity and proved to be safe relative to free DOX (Singh et al, 2017).…”

Section: Gene-targeting Cancer Therapymentioning

confidence: 93%

Drug-loaded PEG-PLGA nanoparticles for cancer treatment

et al. 2022

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Nanoparticles based on single-component synthetic polymers, such as poly (lactic acid-co-glycolic acid) (PLGA), have been extensively studied for antitumor drug delivery and adjuvant therapy due to their ability to encapsulate and release drugs, as well as passively target tumors. Amphiphilic block co-polymers, such as polyethylene glycol (PEG)-PLGA, have also been used to prepare multifunctional nanodrug delivery systems with prolonged circulation time and greater bioavailability that can encapsulate a wider variety of drugs, including small molecules, gene-targeting drugs, traditional Chinese medicine (TCM) and multi-target enzyme inhibitors, enhancing their antitumor effect and safety. In addition, the surface of PEG-PLGA nanoparticles has been modified with various ligands to achieve active targeting and selective accumulation of antitumor drugs in tumor cells. Modification with two ligands has also been applied with good antitumor effects, while the use of imaging agents and pH-responsive or magnetic materials has paved the way for the application of such nanoparticles in clinical diagnosis. In this work, we provide an overview of the synthesis and application of PEG-PLGA nanoparticles in cancer treatment and we discuss the recent advances in ligand modification for active tumor targeting.

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Assessing the targeting and fate of cathepsin k antibody-modified nanoparticles in a rat abdominal aortic aneurysm model

Cited by 13 publications

References 34 publications

The mechanism and therapy of aortic aneurysms

The mechanism and therapy of aortic aneurysms

Inflammatory endothelium-targeted and cathepsin responsive nanoparticles are effective against atherosclerosis

Drug-loaded PEG-PLGA nanoparticles for cancer treatment

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