Overcoming the barriers to optimization of adenovirus delivery using biomaterials: Current status and future perspective.

Adenovirus (Ad) is emerging as a promising modality for cancer gene therapy due to its ability to induce high level of therapeutic transgene expression with no risk of insertional mutagenesis, ability to be facilely produced at a high titer, and capacity to induce robust antitumor immune response. Despite these excellent attributes of human serotype 5 Ad, poor systemic administration capability, coxsackie and adenovirus receptor (CAR)-dependent endocytic mechanism limiting potentially targetable cell types, nonspecific shedding to normal organs, and poor viral persistence in tumor tissues are major hindrances toward maximizing the therapeutic benefit of Ad in clinical setting. To address the abovementioned shortcomings, various non-immunogenic nanomaterials have been explored to modify Ad surface via physical or chemical interactions. In this review, we summarize the recent developments of different types of nanomaterials that had been utilized for modification of Ad and how tumor-targeted local and system delivery can be achieved with these nanocomplexes. Finally, we conclude by highlighting the key features of various nanomaterials-coated Ads and their prospects to optimize the delivery of virus.