Rationally designed nanostructured materials can produce ideal drug carriers that plays 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.
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.
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.
These observations indicate that CS-TPP-(shMTHFD1L-ALA) NPs may be an ideal candidate for gene/photosensitizer delivery.

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