A multi-enzyme cascade antioxidant nano HOF and preparation method and application thereof are provided. The present invention discloses a nano HOF based on selenium-containing ligand for the first time, the nano HOF does not contain metal and has good biocompatibility, which is a universal loading platform, and has high porosity, acid and alkali resistance and thermal stability, and is size-tunable, it can coat various types of enzymes at the same time, stabilize the conformation of the enzyme through the confinement effect, the high porosity can not only provide enough space for the enzyme, but also facilitate the transport of substances and the play of catalytic properties of the enzyme, 85-90% of the activity of the coated enzyme can be maintained, ROS can be effectively scavenged through the cascade catalysis between various enzymes, which provides a new idea for the construction of bio-friendly antioxidants.

Provided herein are compositions, systems, kits, and methods for treating a patient with a thromboembolism by administering nanoconjugates comprising nanoparticles encapsulating and/or conjugated to: i) tissue-type plasminogen activator (tPA), and ii) at least one antioxidant enzyme selected from the group consisting of: superoxide dismutase, glutathione peroxidase, glutathione reductase, and a catalase.

Provided herein are compositions, systems, kits, and methods for treating a patient with a thromboembolism by administering nanoconjugates comprising nanoparticles encapsulating and/or conjugated to: i) tissue-type plasminogen activator (tPA), and ii) at least one antioxidant enzyme selected from the group consisting of: superoxide dismutase, glutathione peroxidase, glutathione reductase, and a catalase.

Disclosed herein are compositions comprising agents that inhibit or prevent the oxidation of one or more cysteine resides in ovarian tumor deubiquitinase (OTUB1) as well as methods of using the compositions, for example, to treat cancers (e.g., lung cancers). Also provided herein are kits comprising the agents.