Chitosan-tripolyphosphate nanoparticles-mediated co-delivery of MTHFD1L shRNA and 5-aminolevulinic acid for combination photodynamic-gene therapy in oral cancer

Photodiagnosis Photodyn Ther. 2021 Dec:36:102581. doi: 10.1016/j.pdpdt.2021.102581. Epub 2021 Oct 12.

Abstract

Background: Rationally designed nanostructured materials can produce improved drug carriers that play an increasingly important role in cancer treatment. In comparison with conventional drug combination approaches, using co-delivery systems of multiple drugs achieves sophisticated targeting strategies and multifunctionality.

Methods: First, a nano-co-delivery of chitosan/tripolyphosphate (CS-TPP) was synthesized and characterized combining 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) shRNA. In this report, we investigated the efficacy of the simultaneous delivery of shRNA/photosensitizer on the gene expression of oral squamous cell carcinoma (OSCC) cells. The efficacy of CS-TPP-(shMTHFD1L-ALA)-PDT in inducing apoptosis and in generating of reactive oxygen species (ROS) in vitro was then assessed by Annexin V-PI and DCFH-DA assays respectively. In vivo therapeutic experiments were conducted in well-established orthotopic animal models of HNSCC.

Results: The results showed that the CS-TPP-(shMTHFD1L-ALA) nanoparticles (NPs) were approximately 145 nm in size. The cytotoxicity of OSCC cells was significantly increased by co-delivery of MTHFD1L shRNA and ALA-PDT compared with other groups. Furthermore, individual and combined therapies revealed remarkable pro-apoptotic, ROS and anti-tumorigenesis effects, and CS-TPP-(shMTHFD1L-ALA)-PDT had additive effects in vitro and in vivo.

Conclusion: These observations indicate that CS-TPP-(shMTHFD1L-ALA) NPs may be an ideal candidate for gene/photosensitizer delivery.

Keywords: Chitosan; Gene therapy; Nanoparticles; Oral squamous cell carcinoma; Photodynamic therapy.

MeSH terms

  • Aminolevulinic Acid / therapeutic use
  • Animals
  • Carcinoma, Squamous Cell* / drug therapy
  • Cell Line, Tumor
  • Chitosan* / analogs & derivatives
  • Genetic Therapy
  • Head and Neck Neoplasms* / drug therapy
  • Mouth Neoplasms* / drug therapy
  • Nanoparticles*
  • Photochemotherapy* / methods
  • Photosensitizing Agents / therapeutic use
  • RNA, Small Interfering

Substances

  • Photosensitizing Agents
  • RNA, Small Interfering
  • chitosan-tripolyphosphate
  • Aminolevulinic Acid
  • Chitosan