Localized chemo-immunotherapy for HNSCC via CpG-synergized doxorubicin release from injectable TPGS/Na₂CO₃ hydrogel remodeling tumor immunity
Source abstract
Abstract
Background Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) exhibit poor survival due to tumor microenvironment (TME) barriers and systemic toxicity of chemo-immunotherapy associated with chemo-immunotherapy. Methods An injectable thermoresponsive hydrogel was engineered by crosslinking D-α-tocopheryl polyethylene glycol succinate (TPGS) with Na₂CO₃ (15 % w/v TPGS: 9 % w/v Na₂CO₃). This platform co-encapsulated doxorubicin-loaded nanoparticles (DOX NP) synthesized via PEI-cis-aconitic acid conjugation and CpG-loaded adjuvant nanoparticles (CpG NP) prepared through genipin-mediated PEI crosslinking. The hydrogel exhibited rapid temperature-triggered gelation, shear-thinning injectability, and a macroporous architecture that enabled dual drug retention and immune cell infiltration. Results In vitro, the hydrogel provided the sustained release of DOX NP with pH-responsive acceleration in acidic TME. In vivo, localized delivery of Gel-DOX NP-CpG NP significantly suppressed tumor growth (p < 0.05) and enhanced cytotoxic CD8+ T-cell infiltration in TME (3.1-fold) and spleens (2.4-fold). RNA sequencing revealed 88 immune-related differentially expressed genes, including downregulated immunosuppressors and enriched cytokine pathways. Conclusion This TPGS/Na₂CO₃ hydrogel platform coordinates chemotherapy-induced immunogenic cell death (DOX NP) with CpG-driven innate immunity, overcoming TME barriers to enhance localized and systemic anti-tumor responses in HNSCC.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoplatforms for cancer theranostics · Cancer Research and Treatments · Immune cells in cancer
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
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