Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy

Abstract

Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.

Breast Cancer Chemo-immunotherapy through Liposomal Delivery of an Immunogenic Cell Death Stimulus Plus Interference in the IDO-1 Pathway

“…44,64 It is also possible to induce ICD through the use of physicochemical stimuli, such as ionizing radiation or photodynamic therapy. 65 Here, we demonstrate the use of a liposomal carrier to induce ICD at an orthotopic BC tumor site, an outcome that is not accomplishable with free DOX (Figure 9B).…”

Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells

“…[92, 93] In PDT treatment, photosensitizing agents are exposed to a particular wavelength of light, generating reactive oxygen species (ROS) that kill nearby cells. [94] Through the use of nanosized carriers, photosensitizing agents can be transported to the tumor site, and subsequently activated.…”

“…[88] Additionally, core-shell NPs, carrying oxaliplatin in the core and PDT-activatable pyrolipid in the shell (NCP@pyrolipid) have proven, when combined with anti-PD-L1 therapy, to be effective at inducing potent tumor-specific immune responses. [93] PDT combined with anti-PD-L1 therapy appears to have a synergistic effect. Furthermore, PDT with NPs and CTLA-4 blockade eliminated tumors upon exposure to near-infrared irradiation.…”

Injecting Nanoparticles into Immunotherapy

“…They used that process to generate an immune response, which, when combined with checkpoint inhibitors, prevented metastases and largely eliminated unirradiated distant tumors (1). When the nanoparticles were loaded with oxaliplatin, an approved chemotherapeutic, and administered in a mouse model of colon cancer, both primary and distant tumors largely disappeared (2). Lin has founded a biotech company, RiMO Therapeutics, with hopes to move these nanoparticles into clinical testing.…”