《Advanced Materials》Mitochondria‑Targeted Pyroptosis‑Augmented Immunoradiotherapy for Melanoma
(1) Journal Source: Advanced Materials
(2) Title: Mitochondria‑Targeted Pyroptosis Orchestrated by Photodynamic Microneedle Patches Potentiates Melanoma Immunoradiotherapy
(3) Research Idea: This paper designs mitochondria‑targeted photodynamic microneedle patches. Upon photoactivation, reactive oxygen species are generated in the mitochondrial region of tumor cells to initiate GSDME‑mediated pyroptosis. Meanwhile, mitochondrial respiration is disrupted to relieve tumor hypoxia. Combined with X‑ray radiotherapy, the tumor immune microenvironment is remodeled to activate systemic antitumor immunity, thereby exerting inhibitory effects on primary tumors and distant metastatic lesions.
(4) Innovations: Integrating mitochondria‑targeted photosensitizers with dissolvable microneedle delivery systems; triggering pyroptosis via mitochondria‑confined oxidative stress to evade apoptosis resistance in melanoma; achieving tumor hypoxia alleviation and radiosensitization simultaneously through mitochondrial damage; inducing in‑situ immune activation by local intervention to produce abscopal antitumor effects.
(5) Material Development
(1) Materials: A dicationic mitochondria‑targeted photosensitizer mitoTPS is constructed based on the BODIPY scaffold; dissolvable microneedle patches mitoTPS‑MNs are fabricated using hyaluronic acid as the matrix.
(2) Functions: mitoTPS can selectively accumulate in mitochondria and efficiently generate singlet oxygen under light irradiation. Transdermal delivery by mitoTPS‑MNs achieves local drug enrichment at lesion sites. Upon light exposure, it triggers mitochondrial damage and pyroptosis, and synergizes with radiotherapy to realize tumor suppression and immune activation.
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