Theranostic
nanoagents are promising for precision medicine. However,
biodegradable nanoagents with the ability for photoacoustic (PA) imaging
guided photothermal therapy (PTT) are rare. We herein report the development
of biodegradable semiconducting polymer nanoparticles (SPNs) with
enhanced PA and PTT efficacy for cancer therapy. The design capitalizes
on the enzymatically oxidizable nature of vinylene bonds in conjunction
with polymer chemistry to synthesize a biodegradable semiconducting
polymer (DPPV) and transform it into water-soluble nanoparticles (SPNV).
As compared with its counterpart SPN (SPNT), the presence of vinylene
bonds within the polymer backbone also endows SPNV with a significantly
enhanced mass absorption coefficient (1.3-fold) and photothermal conversion
efficacy (2.4-fold). As such, SPNV provides the PA signals and the
photothermal maximum temperature higher than SPNT, allowing detection
and photothermal ablation of tumors in living mice in a more sensitive
and effective way. Our study thus reveals a general molecular design
to enhance the biodegradability of optically active polymer nanoparticles
while dramatically elevating their imaging and therapeutic capabilities.