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 a 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 the aptamer
with PEG5000-azobenzene-NHS, which is responsive to hypoxia,
here acting as a caging moiety of conditional recognition. More specifically,
the caging moiety is unresponsive in the intact conjugate and prevents
target recognition. However, in the presence of sodium dithionite
or hypoxia (<0.1% O2) or in the tumor microenvironment,
the caging moiety responds by allowing conditional recognition of
the cell-surface target, thereby reducing the chance of on-target
off-tumor effects. It is also confirmed that the strategy can be used
for developing a conditional antibody. Therefore, this study demonstrates
an efficient strategy by which to develop aptamer/antibody-based diagnostic
probes and therapeutic drugs for cancers with a unique hypoxic microenvironment.
An upconverting covalent organic framework nanoplatform is designed for the first time for the near-infrared activated in situ self-reporting of photodynamic therapy in vivo.
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