(1) Journal Source:
Advanced Functional Materials (2026)
(2) Title:
Biomimetic Hybrid-Membrane Nanoreactor for Deep-Seated Photodynamic Immunotherapy of Hepatocellular Carcinoma via Dual Catalysis-Enhanced ROS Amplification and cGAS-STING Activation
(3) Research Idea:
In this work, a biomimetic self-oxygen-supplying nanoreactor (UMHM) coated with hybrid membranes fused by hepatocellular carcinoma cell membranes and erythrocyte membranes was designed to overcome the bottlenecks of limited light penetration depth, tumor hypoxia and insufficient systemic anti-tumor immunity in photodynamic therapy for deep-seated hepatocellular carcinoma. Under 808 nm near-infrared light irradiation, upconversion nanoparticles in this system are excited to activate photosensitizers for deep photodynamic therapy. Meanwhile, the manganese oxide shell catalyzes oxygen production in the tumor microenvironment to alleviate hypoxia and triggers chemodynamic therapy for synergistically amplified oxidative stress. In addition, the nanoreactor induces immunogenic cell death to release double-stranded DNA, which together with the concomitantly released manganese ions activates the cGAS-STING pathway, thereby remodeling the immunosuppressive tumor microenvironment and eliciting systemic anti-tumor immune responses.
(4) Material Development:
• (1) Material: UCNP@MnOx-Hyp@HRM (abbreviated as UMHM), a core-shell-membrane ternary nanoreactor. Rare-earth-doped upconversion nanoparticles (UCNP) serve as the core. A mixed-valence manganese oxide (MnOx) shell is deposited in situ, and hypericin (Hyp), a photosensitizer, is loaded. The outermost layer is wrapped with a biomimetic hybrid membrane (HRM) fused by hepatocellular carcinoma cell membranes and erythrocyte membranes.
• (2) Functions: It possesses homologous tumor targeting and immune evasion capacities; it converts 808 nm near-infrared light into visible light to activate photosensitizers; it consumes endogenous hydrogen peroxide to produce oxygen in situ and relieve hypoxia; it generates hydroxyl radicals via Fenton-like reactions; it degrades and releases manganese ions and drugs in response to the tumor microenvironment, simultaneously realizing photodynamic/chemodynamic therapy and potent immune adjuvant effects.
(5) Innovations:
1. Innovative Delivery Strategy: A biomimetic hybrid membrane fused by tumor cell membranes and erythrocyte membranes is adopted to combine homologous targeted recognition with long-cycle immune evasion, breaking the functional limitations of single-membrane modification.
2. Multistage Cascade Therapeutic Mechanism: Upconversion luminescence-mediated deep photodynamic therapy is coupled with MnOx-mediated chemodynamic therapy, and local oxidative stress injury is synergistically amplified through dual catalysis.
3. Remodeling of Immune-Activated Microenvironment: The double-stranded DNA released from treatment-triggered immunogenic cell death acts in spatiotemporal synergy with responsively released Mn²⁺ to efficiently activate the cGAS-STING immune signaling pathway, realizing the conversion of "cold tumors" into "hot tumors" and the inhibition of distant metastasis.


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