2026-10-14T05:12:23Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34033708 2026-09-30T16:04:54Z category_4 category_146 category_7 category_8 category_12 category_14 category_19 category_873 category_46 category_61 portal_63 item_type_6 month_year_09_2026

In Situ-Forming Bioresponsive Liposome-Anchored Hydrogel Restores Redox-Immune Homeostasis in Mucosal Macrophages for Radiation-Induced Rectal Injury Repair Hong Wen (662801) Wei Tao (410556) Yuanyuan Fu (510417) Menghuan Li (1589515) Liqi Li (333968) Dong Xiong (15419493) Yanze Kan (16674127) Wensheng Wang (142516) Peng Wang (34436) Zhong Luo (543709) Weidong Xiao (466400) Biochemistry Space Science Medicine Microbiology Cell Biology Molecular Biology Pharmacology Chemical Sciences not elsewhere classified Immunology Developmental Biology undergo temperature transition induced rectal injury forming bioresponsive liposome associated macrophage state associated acute inflammation major pathological driver enabled ros scavenging effective treatment remains findings corroborate lip inflammatory mucosal macrophage sting inhibitor h151 effective rri repair sting inhibition major challenge local ros mucosal macrophages rri treatment upregulated il subsequently activated severely affects selectively taken promising strategy prevalent complication pf127 gel pelvic radiotherapy life quality intestinal fibrosis immune homeostasis immune dyshomeostasis facilely administered conjugated onto chronic fibrosis anchored hydrogel 10 expression Radiation-induced rectal injury (RRI) is a prevalent complication of pelvic radiotherapy that severely affects the life quality of patients, but its effective treatment remains a major challenge in the clinic. Herein, we identify that the redox-immune dyshomeostasis of mucosal macrophages as a major pathological driver of RRI-associated acute inflammation and chronic fibrosis and developed an in situ forming reactive oxygen species (ROS)-responsive liposome-anchored hydrogel (Lip@H151@TK-PF127 Gel) for effective RRI repair. For this purpose, liposomes were further grafted with mannose moieties via thioketal (TK) linkers for loading cGAS-STING inhibitor H151, which were further conjugated onto the TK-PF127 Gel. The Lip@H151@TK-PF127 Gel precursors could be facilely administered to the RRI site via enema and undergo temperature transition to achieve in situ gelation, which would be subsequently activated by local ROS to trigger Lip-TK-Man@H151 release. Lip-TK-Man@H151 could be selectively taken up by inflammatory mucosal macrophage and skew them toward the anti-inflammatory and repair-associated macrophage state through restoring redox-immune homeostasis via cooperative TK-enabled ROS scavenging and cGAS-STING inhibition, hallmarked by upregulated IL-10 expression. Owing to these merits, the Lip@H151@TK-PF127 Gel treatment effectively ameliorated the acute epithelial damage post irradiation while abrogating the risk of intestinal fibrosis in vivo. These findings corroborate Lip@H151@TK-PF127 Gel as a promising strategy for RRI treatment in the clinic. 2026-09-30T00:00:00Z Text Journal contribution 10.1021/acsnano.6c11770.s001 https://figshare.com/articles/journal_contribution/In_Situ-Forming_Bioresponsive_Liposome-Anchored_Hydrogel_Restores_Redox-Immune_Homeostasis_in_Mucosal_Macrophages_for_Radiation-Induced_Rectal_Injury_Repair/34033708 CC BY-NC 4.0