Programming of in Situ Tumor Vaccines via Supramolecular Nanodrug/Hydrogel Composite and Deformable Nanoadjuvant for Cancer Immunotherapy

Nano Lett. 2024 Jul 24;24(29):9017-9026. doi: 10.1021/acs.nanolett.4c02113. Epub 2024 Jul 15.

Abstract

The development of in situ tumor vaccines offers promising prospects for cancer treatment. Nonetheless, the generation of plenary autologous antigens in vivo and their codelivery to DC cells along with adjuvants remains a significant challenge. Herein, we developed an in situ tumor vaccine using a supramolecular nanoparticle/hydrogel composite (ANPMTO/ALCD) and a deformable nanoadjuvant (PPER848). The ANPMTO/ALCD composite consisted of β-cyclodextrin-decorated alginate (Alg-g-CD) and MTO-encapsulated adamantane-decorated nanoparticles (ANPMTO) through supramolecular interaction, facilitating the long-term and sustained production of plenary autologous antigens, particularly under a 660 nm laser. Simultaneously, the produced autologous antigens were effectively captured by nanoadjuvant PPER848 and subsequently transported to lymph nodes and DC cells, benefiting from its optimized size and deformability. This in situ tumor vaccine can trigger a robust antitumor immune response and demonstrate significant therapeutic efficacy in inhibiting tumor growth, suppressing tumor metastasis, and preventing postoperative recurrence, offering a straightforward approach to programming in situ tumor vaccines.

Keywords: cancer immunotherapy; deformable nanoadjuvant; in situ tumor vaccine; lymph node transportation; supramolecular composite.

MeSH terms

  • Adamantane / chemistry
  • Adamantane / therapeutic use
  • Adjuvants, Immunologic* / administration & dosage
  • Adjuvants, Immunologic* / chemistry
  • Adjuvants, Immunologic* / pharmacology
  • Adjuvants, Immunologic* / therapeutic use
  • Alginates / chemistry
  • Animals
  • Cancer Vaccines* / administration & dosage
  • Cancer Vaccines* / chemistry
  • Cancer Vaccines* / immunology
  • Cancer Vaccines* / therapeutic use
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Humans
  • Hydrogels / chemistry
  • Immunotherapy* / methods
  • Mice
  • Nanoparticles* / chemistry
  • Neoplasms / immunology
  • Neoplasms / therapy
  • beta-Cyclodextrins / chemistry

Substances

  • Cancer Vaccines
  • Adjuvants, Immunologic
  • Hydrogels
  • beta-Cyclodextrins
  • Alginates
  • Adamantane