Specific photoacoustic cavitation through nucleus targeted nanoparticles for high-efficiency tumor therapy

As a new type of cancer treatment, photoacoustic (PA) therapy is based on PA shockwave for rapid, selective and effective killing of cancer cells. The nucleus has been widely used as a target for tumor therapy, which has obtained a very considerable therapeutic effect. In situ destruction of tumor cell nucleus by photoacoustic therapy has not been studied. In this paper, a highly efficient nucleus-targeted photoacoustic theranostic polymer was developed for fluorescence and photoacoustic dual-mode imaging-guided PA therapy. The prepared polymer consists of nucleus targeting TAT peptide (TAT: YGRKKRRQRRR), hydrophilic chain poly (N,N-dimethylacrylamide) (PDMA), and near-infrared (NIR) light absorbing agent (hCyR), which can self-assemble to form nanoparticles of approximately 28 nm (denoted as TAT-PDMA-hCyR NPs). The designed nanoparticles show excellent nucleus targeting and tumor cell death (up to 80%) caused by DNA damage under pulsed laser irradiation compared to non-nucleus target counterpart PDMA-hCyR NPs without TAT peptide in vitro. As expected, the fluorescence and PA dual-mode imaging observed that TAT-PDMA-hCyR NPs were able to passively target and enrich in tumors, providing an experimental basis for in vivo treatment and thus ensuring a significant tumor inhibition rate (about 92%). In conclusion, this study provides a new and practicable method for the development of nucleus-targeting nanoparticles as potential theranostic agent for in vivo cancer imaging and therapy.