Asian Journal of Pharmaceutical Sciences
Revamping anti-cGAS-STING therapy via an injectable thermo-responsive supramolecular hydrogel for pathological retinal angiogenesis
doi.org/10.1016/j.ajps.2024.100969
Retinal neovascularization is a leading cause of blindness. While current anti-VEGF drugs effectively inhibit pathological angiogenesis, some patients develop resistance or reduced responsiveness to treatments over time, leading to diminished effectiveness. In this study, we identified high activation of the cGAS-STING signaling pathway, which exacerbated pathological neovascularization and vessel leakage. We developed an injectable thermo-responsive supramolecular hydrogel loaded with an anti-STING drug. The hydrogel, made of Pluronic F127 demonstrated excellent transparency and biocompatibility. Importantly, the thermo-sensitive property allowed for precise spatial release of the drug, extending the effective treatment duration of C-176, which suppressed STING activation in the retina, reduced inflammation and protected retinal tissue. HydroC-176 effectively inhibited microglial cell infiltration and the release of inflammatory angiogenic factors, highlighting its enhanced efficacy. While demonstrating slightly lower effectiveness compared to traditional anti-VEGF therapy, HydroC-176 exhibited more robust capabilities in regulating ocular microenvironmental inflammation. This approach may assist in enhancing the sensitivity and effectiveness of anti-VEGF therapy for reducing ocular inflammation, potentially improving patients’ response to traditional treatment. These results have suggested innovative and comprehensive strategies for the management of retinal neovascularization.视网膜新生血管是失明的主要原因。虽然目前的抗VEGF药物有效地抑制了病理性血管生成，但随着时间的推移，一些患者对治疗产生了耐药性或反应性降低，导致疗效降低。在这项研究中，我们发现cGAS STING信号通路的高度激活加剧了病理性血管新生和血管渗漏。我们开发了一种负载抗STING药物的可注射热响应超分子水凝胶。由Pluronic F127制成的水凝胶显示出优异的透明度和生物相容性。重要的是，热敏特性允许药物的精确空间释放，延长了C-176的有效治疗时间，从而抑制了视网膜中的STING激活，减少了炎症并保护了视网膜组织。HydroC-176有效地抑制了小胶质细胞浸润和炎性血管生成因子的释放，突出了其增强的疗效。虽然与传统的抗VEGF疗法相比，HydroC-176的疗效略低，但在调节眼部微环境炎症方面表现出更强大的能力。这种方法可能有助于提高抗VEGF治疗的敏感性和有效性，以减少眼部炎症，从而可能改善患者对传统治疗的反应。这些结果为视网膜新生血管的管理提出了创新和全面的策略。
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