Cancer-cell-biomimetic Upconversion nanoparticles combining chemo-photodynamic therapy and CD73 blockade for metastatic triple-negative breast cancer

Abstract

Photodynamic therapy (PDT) and chemotherapy show clinical promise in destroying orthotopic tumors but are insufficient against abscopal metastases. The research reports the combined application of an anti-CD73 antibody and chemo-PDT to synergistically amplify the anti-metastatic effects of T cell-mediated antitumor immunity. The cancer cell membrane (CM)-cloaked upconversion nanoparticles, integrating rose bengal (RB) and the reactive oxygen species (ROS)-sensitive polymer polyethylene glycol-thioketal-doxorubicin (PEG-TK-DOX, i.e., PTD), are tailored for near-infrared (NIR)-triggered chemo-PDT. CM camouflage enables nanoparticles' excellent tumor-targeting abilities and immune escape from macrophages. The combination of PDT and chemotherapy presents strong synergistic antitumor efficacy and synchronously causes a series of immunogenic cell death (ICD), leading to tumor-specific immunity. The anti-CD73 antibody prevents the immunosuppression phenomenon in tumors by blocking the adenosine pathway, and it is emerging as a sufficient immune checkpoint blockade when combined with ICD-elicited tumor therapies. As cancer membrane camouflaged nanoparticles CM@UCNP-RB/PTD combined with anti-CD73 antibodies, synergistic efficacy of chemotherapy and PDT not only destroys the orthotopic tumors by DOX and cytotoxic ROS but also prevents abscopal tumor metastasis via inducing systemic cytotoxic T cell responses with CD73 blockade. This strategy is promising in curing metastatic triple-negative breast cancer in preclinical research.

Keywords: Antitumor immunity; CD73 blockade; Cancer cell membranes; Chemo-photodynamic therapy; Tumor metastasis.