(1) Journal Source: Advanced Functional Materials


(2) Title: Injectable Thermosensitive Hydrogel Encapsulated Manganese-Coordinated Liposomes for Synergistic STING Pathway Amplification and Postoperative Tumor Immunotherapy


(3) Research Highlights: In this work, an injectable thermosensitive hydrogel-encapsulated manganese-coordinated liposome delivery system, AC@MLip‑IL11 Gel, was designed for co-loading celastrol and the STING agonist ADU‑S100. Manganese ion coordination modification optimizes the physicochemical properties and drug-loading stability of liposomes. Celastrol inhibits the PI3K‑AKT pathway and synergizes with ADU‑S100 to activate the STING‑IRF3 signaling axis, induce immunogenic cell death in tumor cells, promote the maturation of dendritic cells, increase the infiltration of cytotoxic T cells, and remodel the local immune microenvironment of postoperative tumors.


(4) Innovations: ① Liposomes are constructed via a manganese ion-DOPA coordination strategy to improve drug retention capacity; ② Celastrol and the STING agonist form a synergistic combination that simultaneously inhibits the pro-tumor AKT pathway and amplifies STING immune signals; ③ Liposomes are dispersed in a thermosensitive hydrogel to achieve long-term in situ sustained release; ④ The inhibitory effects of this system on local lesions and distant metastatic lesions are investigated in a tumor resection postoperative model.


(5) Material Development (1) Materials: DSPC, DOPA, cholesterol, and DSPE‑PEG‑IL11 are used to construct manganese-coordinated liposomes co-loaded with celastrol and ADU‑S100, which are formulated into the thermosensitive injectable hydrogel AC@MLip‑IL11 Gel. (2) Functions: It features temperature-responsive sol-gel transition and pH-responsive drug release; it can sustainably release dual drugs in situ, induce tumor cell apoptosis and immunogenic cell death, activate the STING pathway, and facilitate antigen presentation and anti-tumor immune responses.

(6) Extended Perspectives: This manganese-coordinated liposome-thermosensitive hydrogel scaffold can be adapted to other immune agonists and pathway inhibitors. The types of coordinating metals and lipid components can be further optimized to regulate the timing of pathway activation. It can be extended to other tumor models requiring local postoperative immune intervention.

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