Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 5, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202113506
Keywords
aggregation; phthalocyanine-artesunate; sonodynamic therapy; synergistic effect; ultrasonic cavitation
Categories
Funding
- National Natural Science Foundation of China [U1705282, 21907015, 22178065]
- Natural Science Foundation of Fujian, China [2019J01204]
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The study designed a novel sonosensitizer ZnPcT(4)A, which exhibited significantly enhanced sonodynamic activity in its aggregated state. This enhancement effect may be attributed to the boosted ultrasonic cavitation of nanostructures, and the level of this effect depends on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Additionally, biological experiments demonstrated that ZnPcT(4)A has high anticancer activity and biosafety.
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. ZnPcT(4)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. ZnPcT(4)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 ZnPcT(4)A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.
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