Light-Activated Nanoparticles Kill Primary Tumors and Distant Metastases

A novel type of nanoparticle carries two anticancer drugs to attack colorectal cancer while simultaneously recruiting and activating T-cells to fight the tumors.

Advanced colorectal cancer is one of the deadliest cancers, with a five-year survival rate of only 12% for patients with the metastatic disease. Checkpoint blockade therapy, which counters biochemical signals transmitted by the cancer cells to suppress the immune system and prevent recognition by T-cells, is among the most promising immunotherapies for patients with advanced colon cancer, but has not been particularly successful. This is due in part to the lack of T-cells inside well-established tumors and the difficulty in attracting T-cells from other parts of the body to the tumor.

Investigators at the University of Chicago (IL, USA) have developed a method to enhance the effectiveness of checkpoint blockade therapy. They developed a novel type of nanoparticle assembled from zinc and the drug oxaliplatin, an agent in regular use against advanced-stage metastatic colon cancer. The photosensitizing agent pyrolipid, which attacks tumors following light activation, was used to coat the outer layer of the particles. The nanoparticles therefore represented a method for the effective delivery of both chemotherapy and photodynamic therapy (PDT).

The effectiveness of the particles when tested in a mouse model was as evidenced by early calreticulin (CRT) exposure on the cell surface, antitumor vaccination, tumor-specific T-cell response, and an abscopal effect. The abscopal effect is usually described with ionizing radiation and refers to regression of a tumor outside of the irradiated volume. Although the mechanism is unknown, it is thought to be immune modulated.

The investigators reported in the August 17, 2016, online edition of the journal Nature Communications that in a mouse model nanoparticle treatment in combination with PD-L1 checkpoint blockade, therapy not only led to the regression of the primary tumors treated locally with light irradiation, but also mediated regression of non-irradiated distant tumors by inducing a strong tumor-specific immune response.

“Everybody out there working in the cancer space is trying to figure out ways to enhance checkpoint blockade immunotherapy,” said senior author Dr. Wenbin Lin, professor of chemistry at the University of Chicago. “In this work, we were able to achieve that. We believe that this combination is able to activate the immune system to generate the T-cells that will recognize the cancer cells. Then they go around the body and kill the cancer cells in the distant site that has not been irradiated with the light.”

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