The
ability to activate drugs only at desired locations avoiding
systemic immunosuppression and other dose limiting toxicities is highly
desirable. Here we present a new approach, named local drug activation,
that uses bioorthogonal chemistry to concentrate and activate systemic
small molecules at a location of choice. This method is independent
of endogenous cellular or environmental markers and only depends on
the presence of a preimplanted biomaterial near a desired site (e.g.,
tumor). We demonstrate the clear therapeutic benefit with minimal
side effects of this approach in mice over systemic therapy using
a doxorubicin pro-drug against xenograft tumors of a type of soft
tissue sarcoma (HT1080)
