PLGA- Astragalus Polysaccharide Nanovaccines Exert Therapeutic Effect in Colorectal Cancer

Int J Nanomedicine. 2024 Sep 12:19:9437-9458. doi: 10.2147/IJN.S479334. eCollection 2024.

Abstract

Background: Tumor vaccines have achieved remarkable progress in treating patients with various tumors in clinical studies. Nevertheless, extensive research has also revealed that tumor vaccines are not up to expectations for the treatment of solid tumors due to their low immunogenicity. Therefore, there is an urgent need to design a tumor vaccine that can stimulate a broad anti-tumor immune response.

Methods: In this work, we developed a nanovaccine (NP-TCL@APS), which includes nanoparticles loaded with colorectal cancer tumor cell lysates (TCL) and Astragalus polysaccharides (APS) into poly (lactic-co-glycolic acid) to induce a robust innate immune response. The NP-TCL@APS was identified by transmission electron microscopy and Malvern laser particle size analyzer. The killing and immune activation effects of NP-TCL@APS were evaluated in vitro. Finally, safety and anti-tumor efficacy were evaluated in the colorectal cancer tumor-bearing mouse model.

Results: We found that NP-TCL@APS was preferentially uptaken by DC and further promoted the activation of DC in vitro. Additionally, nanoparticles codelivery of TCL and APS enhanced the antigen-specific CD8+ T cell response and suppressed the growth of tumors in mouse models with good biocompatibility.

Conclusion: We successfully prepared a nanovaccine termed NP-TCL@APS, which can promote the maturation of DC and induce strong responses by T lymphocytes to exert anti-tumor effects. The strategy proposed here is promising for generating a tumor vaccine and can be extended to various types of cancers.

Keywords: Astragalus polysaccharide; PLGA; colorectal cancer; nanovaccine; tumor cell lysates (TCL).

MeSH terms

  • Animals
  • Astragalus Plant / chemistry
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines* / administration & dosage
  • Cancer Vaccines* / chemistry
  • Cancer Vaccines* / immunology
  • Cell Line, Tumor
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / therapy
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / chemistry
  • Nanovaccines
  • Polylactic Acid-Polyglycolic Acid Copolymer* / chemistry
  • Polysaccharides* / administration & dosage
  • Polysaccharides* / chemistry
  • Polysaccharides* / pharmacology

Substances

  • Cancer Vaccines
  • Polysaccharides
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Nanovaccines

Grants and funding

This research was supported by the National Natural Science Foundation of China (NO: 81760437,82160548,82260819), Natural Science Foundation of Ningxia Province (NO:2020AAC03183,2021AAC02011,2023AAC02042,2023AAC02082) and Key Research and Development Program of Ningxia Province (NO: 2023BEG02013).