SMART ADENOVIRUS NANOCOMPLEXES FOR SYSTEMIC DELIVERY

A challenge to develop adenovirus (Ad)-mediated therapeutics has been issued to treat metastatic cancer via systemic administration. For effective gene therapeutics against primary and metastatic lesions, a systemically injectable tumor-targeting Ad vector system must be developed. Systemic delivery of Ad, however, is hampered by immune response against Ad, short half-life in the circulation, liver uptake, and low accumulation at target disease sites. Modification of the Ad surface allows Ad to circulate in the bloodstream for a longer time, to be not targeted to the liver, and to passively accumulate in tumor sites via enhanced permeation and retention effects. The addition of affinity tags results in active targeting and high efficacy. Strategies including addition of polymer complexes, chemical modifications, and targeting moieties have been applied to develop systemically injectable Ad gene therapeutic carriers. More versatile designs of Ad hybrid complexes have been developed with inorganic nanoparticles, polymers, and lipids, making smart nanomedicine possible. Integration of viral and nonviral nanomaterials can substantially synergize both fields, creating a new concept of gene therapeutics. Here, we describe the various Ad hybrid complex systems used to overcome the limited clinical applicability of conventional Ads and enable effective treatment of distant metastatic tumors via systemic injection.