Photoacoustic Cavitation‐Ignited Reactive Oxygen Species to Amplify Peroxynitrite Burst by Photosensitization‐Free Polymeric Nanocapsules

Photoacoustic (PA) technology can transform light energy into acoustic wave, which can be used for either imaging or therapy that depends on the power density of pulsed laser. Here, we report photosensitizer-free polymeric nanocapsules loaded with nitric oxide (NO) donors, namely NO-NCPs, formulated from NIR light-absorbable amphiphilic polymers and a NO-releasing donor, DETA NONOate. Controlled NO release and nanocapsule dissociation are achieved in acidic lysosomes of cancer cells. More importantly, upon pulsed laser irradiation, the PA cavitation can excite water to generate significant reactive oxygen species (ROS) such as superoxide radical (O₂^.- ), which further spontaneously reacts with the in situ released NO to burst highly cytotoxic peroxynitrite (ONOO^- ) in cancer cells. The resultant ONOO^- generation greatly promotes mitochondrial damage and DNA fragmentation to initiate programmed cancer cell death. Apart from PA imaging, PA cavitation can intrinsically amplify reactive species via photosensitization-free materials for promising disease theranostics.