Three-Dimensional Covalent Organic Frameworks with Cross-Linked Pores for Efficient Cancer Immunotherapy.

We report the design and synthesis of a series of three-dimensional (3D) covalent organic frameworks (COFs) as immunogenic cell death (ICD) inducers for cancer immunotherapy. Three triple-topic amine building blocks, inactive to inducing ICD, were used to construct three COFs, COF-607, COF-608, and COF-609, with outstanding ICD eliciting efficiency. Mechanism studies revealed that after linking these ICD inert monomers into the COF backbone, the optical properties of these COFs could be systematically tuned to achieve excellent reactive oxygen species (ROS) production performance. This combined with 3D cross-linked pores, mimicking lung structure, favor the exchange and diffusion of oxygen and ROS, leading to excellent inducing ICD efficacy. One member, COF-609, is capable of triggering abscopal and long-lasting immune memory effects in a mouse model of breast cancer with >95% mice survival after being treated with COF-609+αCD47 for 110 days.

Use of nanotechnology for improved pharmacokinetics and activity of immunogenic cell death inducers used in cancer chemotherapy.

INTRODUCTION: Immunogenic cell death inducers (ICD inducers) are a diverse group of therapeutic molecules capable of eliciting an adaptive immune response against the antigens present on the surface of dying cancer cells. Most of these molecules suffer from low bioavailability, high toxicity and poor pharmacokinetics which limit their application. It is believed that nanotechnology, in particular nano-sized nanocarriers, can address most of the issues that limit the use of ICD inducers. Area covered: The mechanism of action of ICD inducers and their limitations is discussed. In addition, we cover the novel possibilities arising from the use of nanotechnology to improve delivery of ICD inducers to the target tissue as well as the restrictions of modern nanotechnology. Expert opinion: At present, nanocarrier formulations suffer from low bioavailability, poor pharmacokinetics and stability issues. Nonetheless, there is a tremendous future for combinatorial immune-pharmacological treatments of human tumors based on nanocarrier delivery of ICD inducers.