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Programming Injectable DNA Hydrogels Yields Tumor Microenvironment-Activatable and Immune-Instructive Depots for Augmented Chemo-Immunotherapy.
Fan, Yu; Zhan, Mengsi; Liang, Junhao; Yang, Xingsen; Zhang, Beibei; Shi, Xiangyang; Hu, Yong.
Afiliación
  • Fan Y; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, P. R. China.
  • Zhan M; College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, P. R. China.
  • Liang J; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, P. R. China.
  • Yang X; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, P. R. China.
  • Zhang B; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, P. R. China.
  • Shi X; College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, P. R. China.
  • Hu Y; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, P. R. China.
Adv Sci (Weinh) ; 10(29): e2302119, 2023 10.
Article en En | MEDLINE | ID: mdl-37541435
Injectable hydrogels have attracted increasing attention for promoting systemic antitumor immune response through the co-delivery of chemotherapeutics and immunomodulators. However, the biosafety and bioactivity of conventional hydrogel depots are often impaired by insufficient possibilities for post-gelling injection and means for biofunction integration. Here, an unprecedented injectable stimuli-responsive immunomodulatory depot through programming a super-soft DNA hydrogel adjuvant is reported. This hydrogel system encoded with adenosine triphosphate aptamers can be intratumorally injected in a gel formulation and then undergoes significant molecular conformation change to stimulate the distinct release kinetics of co-encapsulated therapeutics. In this scenario, doxorubicin is first released to induce immunogenic cell death that intimately works together with the polymerized cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) in gel scaffold for effectively recruiting and activating dendritic cells. The polymerized CpG ODN not only enhances tumor immunogenicity but minimizes free CpG-induced splenomegaly. Furthermore, the subsequently released anti-programmed cell death protein ligand 1 (aPDL1) blocks the corresponding immune inhibitory checkpoint molecule on tumor cells to sensitize antitumor T-cell immunity. This work thus contributes to the first proof-of-concept demonstration of a programmable super-soft DNA hydrogel system that perfectly matches the synergistic therapeutic modalities based on chemotherapeutic toxicity, in situ vaccination, and immune checkpoint blockade.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hidrogeles / Microambiente Tumoral Idioma: En Revista: Adv Sci (Weinh) Año: 2023 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hidrogeles / Microambiente Tumoral Idioma: En Revista: Adv Sci (Weinh) Año: 2023 Tipo del documento: Article Pais de publicación: Alemania