Tumor microenvironment and intracellular signal-activated nanomaterials for anticancer drug delivery

Cancer-associated stimuli-responsive nanosystems have been increasingly considered for the delivery of anticancer drugs, which primarily target the tumor microenvironment and/or intracellular elements to enhance intratumoral accumulation and promote drug release at the target site. The signals facilitating drug delivery include tumor and endocytic acidities, hypoxia, enzyme overexpression, as well as high levels of intracellular glutathione, reactive oxygen species, and adenosine-5'-triphosphate. This article reviews the current techniques and ongoing developments in anticancer drug delivery using these signals. In particular, the focus is placed on design strategies and methods of formulating novel nanoscaled materials. The merits and drawbacks of recent strategies, as well as potential future developments, are discussed.