Introduction: Adenovirus (Ad) is a promising candidate vector for cancer gene therapy because of its unique characteristics, which include efficient infection, high loading capacity and lack of insertional mutagenesis. However, systemic administration of Ad is hampered by the host's immune response, hepatocytoxicity, short half-life of the vector and low accumulation at the target site. For these reasons, clinical applications of Ad are currently restricted.
Areas covered: In this review, we focus on recent developments in Ad nanocomplex systems that improve the transduction and targeting efficacy of Ad vectors in cancer gene therapy. We discuss the development of different Ad delivery systems, including surface modification of Ad, smart Ad/nanohybrid systems and hydrogels for sustained release of Ad.
Expert opinion: The fusion of bioengineering and biopharmaceutical technologies can provide solutions to the obstacles encountered during systemic delivery of Ads. The in vivo transgene expression efficiency of Ad nanocomplex systems is typically high, and animal tumor models demonstrate that systemic administration of these Ad complexes can arrest tumor growth. However, further optimization of these smart Ad nanocomplex systems is needed to increase their effectiveness and safety for clinical application in cancer gene therapy.