Endogenous dual stimuli-activated NO generation in the conventional outflow pathway for precision glaucoma therapy

Fan, Wenpei; Song, Maomao; Li, Liping; Niu, Liangliang; Chen, Yue; Han, Binze; Sun, Xinghuai; Yáng, Zhèn; Lei, Yuan; Chen, Xiaoyuan

doi:10.1016/j.biomaterials.2021.121074

Cited by 18 publications

(16 citation statements)

References 70 publications

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“…As an important gas transmitter, NO has been demonstrated to affect a variety of physiological processes such as apoptosis, angiogenesis, immune response, and neurotransmission. [87][88][89][90] Thus, NO has been extensively studied in various biomedical applications, including cardiovascular homeostasis, neurotransmission, bone metabolism, respiratory diseases, antimicrobial therapy, wound healing, among others. [91] NO plays a therapeutic role in different diseases through different mechanisms.…”

Section: No-generating Ggnsmentioning

confidence: 99%

The Advancement of Gas‐Generating Nanoplatforms in Biomedical Fields: Current Frontiers and Future Perspectives

et al. 2022

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Diverse gases (NO, CO, H2S, H2, etc.) have been widely applied in the medical intervention of various diseases, including cancer, cardiovascular disease, ischemia‐reperfusion injury, bacterial infection, etc., attributing to their inherent biomedical activities. Although many gases have many biomedical activities, their clinical use is still limited due to the rapid and free diffusion behavior of these gases molecules, which may cause potential side effects and/or ineffective treatment. Gas‐generating nanoplatforms (GGNs) are effective strategies to address the aforementioned challenges of gas therapy by preventing gas production or release at nonspecific sites, enhancing GGNs accumulation at targeted sites, and controlling gas release in response to exogenous (UV, NIR, US, etc.) or endogenous (H2O2, GSH, pH, etc.) stimuli at the lesion site, further maintaining gas concentration within the effective range and achieving the purpose of disease treatment. This review comprehensively summarizes the advancements of “state‐of‐the‐art” GGNs in the recent three years, with emphasis on the composition, structure, preparation process, and gas release mechanism of the nanocarriers. Furthermore, the therapeutic effects and limitations of GGNs in preclinical studies using cell/animal models are discussed. Overall, this review enlightens the further development of this field and promotes the clinical transformation of gas therapy.

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Section: No-generating Ggnsmentioning

confidence: 99%

The Advancement of Gas‐Generating Nanoplatforms in Biomedical Fields: Current Frontiers and Future Perspectives

et al. 2022

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“…For silica nanoparticles, mesoporous silica nanoparticles (MSNs) and xxx were used as carrier for NO donors [ 21 , 22 ]. Compared with nitroprusside (SNP) solution, the SNP@MSN system exhibited more efficacious and long lasting effect in IOP lowering [ 21 ].…”

Section: Nitric Oxide-donating Drugs For Iop Loweringmentioning

confidence: 99%

“…With 1/40 dose, SNP@MSN increased IOP lowering effect from 3 hours to 48 hours. For hollow mesoporous organosilica (HOS) nanocapsules, it was biodegradable and can achieve trans-corneal co-delivery of hydrophobic NO donor JS-K (JR) and hydrophilic NO donor L-Arginine (LO) to the target tissues inside the eye [ 22 ]. HOS-J R L O was endogenous stimuli-responsive and was reduced and oxidized by ascorbic acid and catalysis of eNOS to release a large amount of NO molecules to lower IOP.…”

Section: Nitric Oxide-donating Drugs For Iop Loweringmentioning

confidence: 99%

“…A large amount of NO donors including conventional standalone NO donors, combination NO donors and NO donating nanomedicine have been proven effective in IOP lowering [ 5 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Combination therapies can have synergistic effect on IOP lowering, such as NO-donating prostaglandins, NO donating β-blockers, NO donating carbonic anhydrase inhibitor and the dual NO donor deliver system [ 22 ]. NO donor loaded nanoparticles improved the therapeutic effect and action duration of the conventional NO donor [ 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…Combination therapies can have synergistic effect on IOP lowering, such as NO-donating prostaglandins, NO donating β-blockers, NO donating carbonic anhydrase inhibitor and the dual NO donor deliver system [ 22 ]. NO donor loaded nanoparticles improved the therapeutic effect and action duration of the conventional NO donor [ 20 , 21 , 22 ]. β-gal-NONOate aims to precisely deliver NO in a conventional outflow system [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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The Application of Nitric Oxide for Ocular Hypertension Treatment

Han

Song

et al. 2021

Molecules

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Despite of various therapeutic methods for treating ocular hypertension and glaucoma, it still remains the leading cause of irreversible blindness. Intraocular pressure (IOP) lowering is the most effective way to slow disease progression and prevent blindness. Among the ocular hypotensive drugs currently in use, only a couple act on the conventional outflow system, which is the main pathway for aqueous humor outflow and the major lesion site resulting in ocular hypertension. Nitric oxide (NO) is a commendable new class of glaucoma drugs that acts on the conventional outflow pathway. An increasing number of nitric oxide donors have been developed for glaucoma and ocular hypertension treatment. Here, we will review how NO lowers IOP and the types of nitric oxide donors that have been developed. And a brief analysis of the advantages and challenges associated with the application will be made. The literature used in this review is based on Pubmed database search using ‘nitric oxide’ and ‘glaucoma’ as key words.

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Rapidly Blocking the Calcium Overload/ROS Production Feedback Loop to Alleviate Acute Kidney Injury via Microenvironment‐Responsive BAPTA‐AM/BAC Co‐Delivery Nanosystem

Yan

Wang

Zhang

et al. 2023

Small

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AKI is a common clinical syndrome with manifestations of progressive decrease in glomerular filtration rate to less than 75%, an abnormal increase in creatinine (CRE) and blood urea nitrogen (BUN), and a urine output of less than 0.5 mL kg −1 h −1 . [2] Continued deterioration of renal function to the point of toxin accumulation, dehydration/electrolyte disturbance, and acid-base imbalance can result in acute renal failure with a hospital mortality rate of 50% or more if not treated promptly and thoroughly. [3] Currently, there are no effective therapeutic drugs for the clinical management of AKI, which is primarily treated by hemodialysis or kidney transplantation. However, these supportive means still have a series of disadvantages, including high cost, low patient compliance, and a high incidence of complications. [4] Even though organ transplantation can significantly reduce the mortality rate of AKI, immunological rejection after transplantation requires patients to take immunosuppressive drugs for an extended period of time, resulting in decreased resistance and increased disease risk (hypertension, anemia, arthritis, cancer, etc.). [5] Therefore, there is an urgent need to develop effective drugs for AKI that can rapidly reverse AKI within a short period of time (few hours) and promote renal function recovery in order to prevent complications and improve the survival rate of AKI.The specific pathophysiological process underlying I/Rinduced AKI is as described below: (1) During renal ischemia, the drop in oxygen partial pressure accelerates the degradation of ATP into hypoxanthine. Rapid depletion of ATP causes depolarization of the cell membrane and activation of the Na + -Ca 2+ exchange mechanism, resulting in a substantial influx of extracellular Ca 2+ . [6] (2) After reperfusion, hypoxic cells are reoxygenated, and hypoxanthine accumulated during hypoxia reacts with oxygen molecules to produce large amounts of ROS, which can damage the cell membrane and endoplasmic reticulum (ER), resulting in an influx of extracellular and ER Ca 2+ into the cytoplasm. [7] Ca 2+ deficiency in the lumen of the ER can worsen ER stress (ERS) by disrupting Ca 2+ -dependent chaperone activity and accumulating unfolded proteins, leading to renal cell death Calcium overload and ROS overproduction, two major triggers of acute kidney injury (AKI), are self-amplifying and mutually reinforcing, forming a complicated cascading feedback loop that induces kidney cell "suicide" and ultimately renal failure. There are currently no clinically effective drugs for the treatment of AKI, excluding adjuvant therapy. In this study, a porous siliconbased nanocarrier rich in disulfide bond skeleton (<50 nm) is developed that enables efficient co-loading of the hydrophilic drug borane amino complex and the hydrophobic drug BAPTA-AM, with its outer layer sealed by the renal tubule-targeting peptide PEG-LTH. Once targeted to the kidney injured site, the nanocarrier structure collapses in the high glutathione environment of the early stage of A...

show abstract

Endogenous dual stimuli-activated NO generation in the conventional outflow pathway for precision glaucoma therapy

Cited by 18 publications

References 70 publications

The Advancement of Gas‐Generating Nanoplatforms in Biomedical Fields: Current Frontiers and Future Perspectives

The Advancement of Gas‐Generating Nanoplatforms in Biomedical Fields: Current Frontiers and Future Perspectives

The Application of Nitric Oxide for Ocular Hypertension Treatment

Rapidly Blocking the Calcium Overload/ROS Production Feedback Loop to Alleviate Acute Kidney Injury via Microenvironment‐Responsive BAPTA‐AM/BAC Co‐Delivery Nanosystem

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