Injectable Anti‐Inflammatory Supramolecular Nanofiber Hydrogel to Promote Anti‐VEGF Therapy in Age‐Related Macular Degeneration Treatment

Abstract

Age‐related macular degeneration (AMD) is a major cause of visual impairment and severe vision loss worldwide, while the currently available treatments are often unsatisfactory. Previous studies have demonstrated both inflammation and oxidative‐stress‐induced damage to the retinal pigment epithelium are involved in the pathogenesis of aberrant development of blood vessels in wet AMD (wet‐AMD). Although antivascular endothelial growth factor (VEGF) therapy (e.g., Ranibizumab) can impair the growth of new blood vessels, side effects are still found with repeated monthly intravitreal injections. Here, an injectable antibody‐loaded supramolecular nanofiber hydrogel is fabricated by simply mixing betamethasone phosphate (BetP), a clinic anti‐inflammatory drug, anti‐VEGF, the gold‐standard anti‐VEGF drug for AMD treatment, with CaCl2. Upon intravitreal injection, such BetP‐based hydrogel (BetP‐Gel), while enabling long‐term sustained release of anti‐VEGF to inhibit vascular proliferation in the retina and attenuate choroidal neovascularization, can also scavenge reactive oxygen species to reduce local inflammation. Remarkably, such BetP‐Gel can dramatically prolong the effective treatment time of conventional anti‐VEGF therapy. Notably, anti‐VEGF‐loaded supramolecular hydrogel based on all clinically approved agents may be readily translated into clinical use for AMD treatment, with the potential to replace the current anti‐VEGF therapy.

An immunotherapeutic artificial vitreous body hydrogel to control choroidal melanoma and preserve vision after vitrectomy

“…S25). As expected, the heights of the a and b waves, which are closely associated with the activity of photoreceptor cells, RPE cells, retinal bipolar cells and Müller cells (31), were in the normal range, indicating that our AVB exhibited nearly no effect on the visual function of mice. In contrast, the two mice in the silicone oil group with abnormal eyes showed decreased visual function (a and b waves decreased).…”

“…Among them, immune checkpoint blockade using antibodies to block immune checkpoint pathways, such as the programmed cell death protein 1 pathway (PD-1/PD-L1), has been demonstrated to be an effective strategy in treating different types of cancers in the clinic (27). Considering the existence of complicated ocular structural barriers and low immunogenicity of the choroidal melanoma, intravenous administration of immune checkpoint antagonists is unable to achieve effective therapeutic benefit in previous researches (28), while intraocular injection of antagonists may cause many side effects, such as uveitis, endophthalmitis, and retinal detachment (29)(30)(31). Therefore, it is important to develop a biocompatible material that is able to serve as a vitreous substitute and drug reservoir simultaneously to preserve vision and sustainably release immunotherapeutic drugs to inhibit the recurrence of intraocular malignant tumors after surgical resection.…”

Glutathione-Responsive and Hydrogen Sulfide Self-Generating Nanocages Based on Self-Weaving Technology To Optimize Cancer Immunotherapy

“…Chronological Remodeling of ITME by BetP@HA-gNCs. Based on previous studies, 51 it has been found that BetP can attenuate the inflammation-related nuclear factor κB (NF-κB) signaling pathway by interfering with the p65 translocation of NF-kB to the nucleus. It also suppresses the genetic transcription of proinflammatory cytokines and matrix metalloproteinase (MMP2) related transcription, thus reprogramming the tumor-promoting chronic inflammation.…”

Chemically Modified Platforms for Better RNA Therapeutics

“…142 Especially in wet AMD, excessive VEGF production leads to the formation of abnormal, leaky blood vessels beneath the retina, resulting in damage and scarring that cause rapid vision loss. 143 Notably, Pegaptanib selectively binds to the VEGF165 isoform, the most biologically active form of VEGF in promoting angiogenesis. By binding to VEGF165, 142 Pegaptanib effectively blocks its interaction with the VEGF receptor on endothelial cell surfaces.…”

“…Pegaptanib (Macugen) is the only antiangiogenic RNA aptamer designed to target VEGF in the treatment of AMD (Figure d), which is a progressive eye disorder that primarily affects the macula, the central part of the retina responsible for sharp and central vision and is a leading cause of vision loss in individuals aged 50 and older . Especially in wet AMD, excessive VEGF production leads to the formation of abnormal, leaky blood vessels beneath the retina, resulting in damage and scarring that cause rapid vision loss . Notably, Pegaptanib selectively binds to the VEGF165 isoform, the most biologically active form of VEGF in promoting angiogenesis.…”