Cancer-fighting nanoparticles co-delivering a chemotherapy drug & immunotherapy

Chemotherapy is a pillar of cancer treatment, but residual cancer cells can persist and cause tumor relapse. This process involves a lipid called phosphatidylserine (PS), which is usually found inside the tumor cell membrane's inner layer but migrates to the cell surface in response to chemotherapy drugs. On the surface, PS acts as an immunosuppressant, protecting remaining cancer cells from the immune system.

University of Pittsburgh researchers have designed cancer-fighting nanoparticles that co-deliver a chemotherapy drug and a novel immunotherapy, according to a new Nature Nanotechnology. The new immunotherapy approach silences a gene that the researchers discovered was involved in immunosuppression. When combined with an existing chemotherapy drug and packaged into tiny nanoparticles, the therapy shrunk tumors in mouse models of colon and pancreatic cancer.

The Pitt researchers found that treatment with chemotherapy drugs fluorouracil and oxoplatin led to increased levels of a protein that controls distribution of PS on the cell membrane. This finding suggested that blocking that protein would prevent cancer cells from shunting PS to the cell surface, allowing immune cells to mop up cancer cells that lingered after chemotherapy.

After packaging siRNA and fluorouracil and oxoplatin together into dual-action nanoparticles, the next step was targeting them to tumors.

The researchers decorated the surface of the nanoparticles with chondroitin sulfate and PEG. These compounds help the nanoparticles target tumors and avoid healthy tissue by binding to cell receptors common on both tumor blood vessels and tumor cells and prolonging the length of time they remain in the bloodstream. Hence, Targeting the protein in combination with chemotherapy may represent a novel strategy for the treatment of various types of cancers.

Reference:

Song Li et al, Targeting Xkr8 via nanoparticle-mediated in situ co-delivery of siRNA and chemotherapy drugs for cancer immunochemotherapy, Nature Nanotechnology, DOI 10.1038/s41565-022-01266-2