4.8 Article

Vitamin C supramolecular hydrogel for enhanced cancer immunotherapy

Journal

BIOMATERIALS
Volume 287, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121673

Keywords

Vitamin C; Self -assembly; Supramolecular hydrogel; Drug delivery; Cancer immunotherapy

Funding

  1. National Natural Science Foundation of China [2020YFA0211100]
  2. Natural Science Foundation of Jiangsu Province [91959104, 21927803, 51903182, 51525203, 52103347, 52032008]
  3. China Postdoctoral Science Foundation [BK20190826]
  4. Suzhou Key Laboratory of Nanotechnology and Biomedicine, Collaborative Innovation Center of Suzhou Nano Science and Technology [2020M671583]
  5. 111 Program from the Ministry of Education of China

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This study presents the use of a novel Vitamin C nanofiber hydrogel as a platform for enhanced cancer immunotherapy. The hydrogel not only serves as a reservoir for Vitamin C but also exhibits anti-tumor effects. The encapsulated stimulator of interferon genes (STING) agonist synergistically activates the immune system to inhibit the progression of tumors.
Vitamin C (VitC) has shown great promise to promote cancer immunotherapy, however, its high hydrophilicity makes it quickly excreted, leading to limited therapeutic efficiency even with frequent high-dose administration. Herein, we provide a pioneering report about the employment of VitC amphiphile self-assembled nanofiber hydrogels for enhanced cancer immunotherapy. Specifically, driven by hydrogen bonding and hydrophobic in-teractions, the synthesized VitC amphiphile, consisting of a hydrophilic VitC headgroup and a hydrophobic alkyl chain, could self-assemble into an injectable nanofiber hydrogel with self-healing properties. The formed VitC hydrogel not only serves as a reservoir for VitC but also acts as an effective delivery platform for stimulator of interferon genes (STING) agonist-4 (SA). Interestingly, the VitC hydrogel itself exhibits antitumor effects by upregulating genes related to interferon (IFN) signaling, apoptotic signaling and viral recognition and defense. Moreover, the SA-encapsulated VitC hydrogel (SA@VitC hydrogel) synergistically activated the immune system to inhibit the progression of both local and abscopal tumors.

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