Hypoxia-activated PEGylated aptamer/antibody for cancer imaging with improved specificity

Aptamers and antibodies, as molecular recognition probes, play critical roles in cancer diagnosis and therapy. However, their recognition ability is based on target overexpression in disease cells, not target exclusivity, which can cause on-target off-tumor effects. To address the limitation, we herein report a novel strategy to develop conditional aptamer conjugate which recognizes its cell surface target, but only after selective activation, as determined by characteristics of the disease microenvironment, which, in our model, involve tumor hypoxia. This conditional aptamer is the result of conjugating aptamer with PEG5000-azobenzene-NHS, which is responsive to hypoxia, here, acts as a caging moiety of conditional recognition. More specifically, the caging moiety is unresponsive in the intact conjugate and prevents target recognition. However, upon in the presence of sodium dithionite, hypoxia (<0.1% O2) or in tumor microenvironment, the caging moiety responds by allowing conditional recognition of cell...