Combinatorial cationic lipid-like nanoparticles for efficient intracellular cytotoxic protein delivery

Introduction: Although protein-based drugs have shown success, they have been limited mostly to cytokines, growth factors, enzymes and monoclonal antibodies, all of which function primarily extracellularly. There are a number of diseases, including genetic diseases and cancers, that have the potential to be treated through proteins with an intracellular target. However, proteins alone are not usually able to cross the cell membrane in order to reach their intracellular targets. Hence it is desirable to develop efficient and effective tools as well as strategies that will enable us to deliver therapeutic proteins in their active forms to tumor cells or tissues. Here we present a combinatorial approach for the creation of cationic lipid-like nanoparticles (termed “lipidoids”) to facilitate intracellular cytotoxic protein delivery for the inhibition of tumor cell proliferation.