A Spatiotemporally Controllable DNA Hydrogel Mesh for Focused Antimetastasis Therapy of Cancer

Cancer is one of the most commonly diagnosed diseases
with high
mortality, and approximately 50% of patients are prone to present
metastasis after various treatments. The shedding of circulating tumor
cells (CTCs) during tumor therapy is the root cause of metastasis.
In this work, we proposed a focused antimetastasis therapy strategy
based on a spatiotemporally controllable DNA hydrogel mesh (SNARE:
just like a turtle trapped in the jar) in vivo. The whole treatment
process was performed in the limited space of the SNARE, which realized
the immobilization of CTCs in situ for antimetastasis effects. A stimulus-responsive
reversible drug nanocarrier module and an epithelial cell adhesion
molecule (EpCAM) aptamer recognition module endowed the SNARE with
spatiotemporal controllability for precise tumor cell immobilization.
The SNARE also activated a robust immune performance through overcoming
immune escape, inducing immunogenic cell death, and enhancing the
cGAS-STING pathway to assist the CTC immobilization strategy for a
better antimetastasis efficiency. Moreover, it was found that the
EpCAM aptamer could realize the endogenous PD-L1 regulation through
the epidermal growth factor receptor pathway, and the immunotherapy
efficiency was further intensified by the ordered networks of the
DNA hydrogel. This work provided a focused antimetastasis therapy
strategy for cancer through the immobilization of CTCs in a limited
space, which also gave insight into alternative development approaches
of immune checkpoint inhibitors.