A Photoactivatable\nSelf-Assembled Nanoagonist for\nSynergistic Therapy against Pancreatic Ductal Adenocarcinoma

Immunotherapy\nhas revolutionized the cancer treatment\nparadigm,\nyet efficient immunotherapeutic responses against immune-cold/desert\ncancers remain challenging. Herein, we report that photoactivatable\nnanoagonists yield a potent antitumor synergy of photoimmunotherapy\nagainst pancreatic ductal adenocarcinoma (PDAC). The nanoagonist was\nfabricated by assembling an amphiphilic boron dipyrromethene-derived\npolymer conjugated with a Toll-like receptor agonist via a photocleavable\nlinker and stimulator of interferon genes agonist. The nanoagonist\nenables light-induced generation of reactive oxygen species and on-demand\nrelease of the agonists to yield synergistic photoimmunotherapy. The\nproduced tumor antigens promote dendritic cell maturation, which is\nfurther amplified by these agonists for eliciting adaptive immunity,\naccompanied by apparently abscopal and long-term memory effects. The\nnanoagonist further alleviates the fibrosis of tumor stroma and the\nimmunosuppressive microenvironment, leading to the deep infiltrations\nof clinically used therapeutics and immune cells to yield preferable\ncombinational treatments against PDAC models. These results provide\nvaluable insights into activatable nanoparticles for cancer therapy\nagainst immune-desert cancers.