Aggregation-Enhanced Sonodynamic Activity of Phthalocyanine-Artesunate Conjugates
Peng-Hui Zhao1, Yu-Lin Wu1, Xue-Yan Li1
1College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China.
Abstract:
The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT4 A showed about 60-fold higher sonodynamic ROS generation in the aggregated form than in the disaggregated form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The level of the AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Moreover, biological studies demonstrated that ZnPcT4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.
