Corneal neovasularization (CNV) is one of the leading causes for visual impairment. Dasatinib is a multi-target tyrosine kinase inhibitor, which can inhibit both platelet derived growth factor receptor and Src family kinases. Erianin exhibits excellent anti-inflammatory and anti-angiogenic effects. In this study, dasatinib and erianin were found to synergically inhibit the proliferation, migration and tube formation of Ea.hy926 cells, the three most important cellular processes of CNV. Next, dasatinib and erianin were co-encapsulated in nanostructured lipid carriers (dasa-eri-NLC), which increased the solubility of dasatinib by about 1790 times, increased the solubility of erianin by about 3 times. To improve its retention time on the ocular surface, dasa-eri-NLC was mixed with gellan gum (dasa-eri-NLC-gel), which achieved a sol-gel transformation when got in contact with tears. The dasa-eri-NLC-gel exhibited good rheological properties with shear thinning properties, extended the ocular residence time by more than 6 times, sustained the drug release, improved the corneal permeability of drug and exhibited good biocompatibility. Finally, the in vivo anti-CNV effect was evaluated in an alkaline burned mouse model of CNV, in which, the dasa-eri-NLC-gel significantly impeded the development and pathological changes of CNV, inhibited the expression of TNF-α, VEGF-A, HIF-1α, Src, pSrc in the cornea. In summary, dasa-eri-NLC-gel safely and efficiently delivered dasatinib and erianin to the cornea and exhibited significantly anti-CNV effect via inhibiting various angiogenesis related cytokines or factors. Dasa-eri-NLC-gel showed a great promise for the treatment of CNV and our study laid a solid foundation for future clinical transformation.

Introduction:The effect of traditional treatment for melanoma is quite limited, especially for its recurrence. As the major components of yeast cell wall, chitin and β-glucan exhibit good immune activation effect and are promising candidates for adjuvant. Therefore, melanoma cell membrane (CM) and indocyanine green (ICG) was loaded in a chitin and β-glucan hybrid hydrogel to achieve an enhanced anti-melanoma therapy.Methods:The novel hybrid hydrogel was prepared, and its physicochemical properties were examined. Its effect towards melanoma prevention and treatment was evaluated via a melanoma-bearing mice model.Results:The CM-ICG-hybrid hydrogel was successfully prepared with excellent injectability, self-healing, drug loading, rheological, in vitro and in vivo photothermal stability, and retention properties. It also exhibited good cellular and in vivo safety profiles. In the primary melanoma mice model, it quickly ablated the in-situ melanoma, effectively inhibited the tumor growth, increased the survival rate of melanoma-bearing mice, and increased the level of IFN-γ and TNF-α. In the distal secondary melanoma model, it efficiently prevented the reoccurrence of melanoma and activated the memory T cells. In both models, a synergistic effect of photothermal therapy and immune therapy was found. The hydrogel effectively recruited CD3+ CD4+ T cells and CD3+ CD8+ T cells, inhibited the proliferation of melanoma cells, and induced the apoptosis of melanoma cells.Conclusion:The hybrid hydrogel was successfully prepared, and it showed excellent efficacy towards melanoma prevention and treatment due to its efficient tumor ablation and immune activation capability.

Introduction:Hepatic ischemia-reperfusion injury (HIRI) is the main reason for liver dysfunction or failure after liver resection and liver transplantation. As excess accumulation of reactive oxygen species (ROS) is the leading factor, ceria nanoparticle, a cyclic reversible antioxidant, is an excellent candidate for HIRI.Methods:Manganese doped mesoporous hollow ceria nanoparticles (MnOx-CeO2 NPs) were prepared, and the physicochemical characteristics, such as particle size, morphology, microstructure, etc. were elucidated. The in vivo safety and liver targeting effect were examined after i.v. injection. The anti-HIRI was determined by a mouse HIRI model.Results:MnOx-CeO2 NPs with 0.40% Mn doped exhibited the strongest ROS-scavenging capability, which may due to the increased specific surface area and surface oxygen concentration. The nanoparticles accumulated in the liver after i.v. injection and exhibited good biocompatibility. In the HIRI mice model, MnOx-CeO2 NPs significantly reduced the serum ALT and AST level, decreased the MDA level and increased the SOD level in the liver, prevent pathological damages in the liver.Conclusion:MnOx-CeO2 NPs were successfully prepared and it could significantly inhibit the HIRI after i.v. injection.

Non-functional scars commonly form after cutaneous injuries. At present, most clinical treatments for scar eradication typically have long treatment courses, low curative effects, and are expensive. In this research, three hydrogels, namely chitin hydrogel, β-glucan hydrogel, and hybrid hydrogel composed of chitin and β-glucan, were successfully prepared, and they exhibited good shear thinning property and bioadhesiveness. In a full-thickness skin defect mouse model, the three hydrogels were found to effectively promote wound closure and inhibit scar formation. Through the immunohistochemistry staining and immunofluorescence staining of the wound tissues, the hydrogels could significantly promote the formation of collagen III, the regeneration of hair follicles, and the expression of keratin K14 and K15. They could also regulate the production of VEGF and immune factors such as IL-10 and IL-12, and inhibit the expression of the fibroblast regulatory factor En-1 in the wound site, which correlated well with their improved wound healing promoting effect and anti-scarring effect. Among all the hydrogels, the hybrid hydrogel was the best to promote wound healing and inhibit scarring. This study, for the first time, proved the excellent therapeutic effect of chitin and β-glucan hydrogels in the management of wound healing and skin regeneration without scar formation, which will lay a solid foundation for the development of skin regeneration medication and future clinical transformation.