Journal
MACROMOLECULAR BIOSCIENCE
Volume 19, Issue 4, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201800365
Keywords
intracellular distribution; nanocapsule; sonodynamic therapy; sonosensitizer
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [26107715]
- Joint Usage/Research Program on Zero-Emission Energy Research, Institute of Advanced Energy, Kyoto University [ZE30B-01]
- Grants-in-Aid for Scientific Research [26107715] Funding Source: KAKEN
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Sonodynamic therapy (SDT) is a novel promising noninvasive therapy involving utilization of low-intensity ultrasound and sonosensitizer, which can generate reactive oxygen species (ROS) by sonication. In SDT, a high therapeutic effect is achieved by intracellular delivery and accumulation at the target sites of sonosensitizer followed by oxidative damage of produced ROS by sonication. Here, pH- and redox-responsive hollow nanocapsules are prepared through the introduction of disulfide cross-linkages to self-assembled polymer vesicles formed from polyamidoamine dendron-poly(l-lysine) for the efficient delivery of sonosensitizer. As sonosensitizer, doxorubicin (DOX), an anticancer drug accumulating into cell nucleus, is selected. Also, the conjugate of DOX and triphenylphosphonium (TPP-DOX) is synthesized as sonosensitizer with mitochondrial targeting ability. DOX and TPP-DOX are delivered to nucleus and mitochondria by nanocapsules. Furthermore, DOX- or TPP-DOX-loaded nanocapsules exhibit in vitro sonodynamic therapeutic effect to HeLa cells with sonication, which might be through oxidative damage to nucleus and mitochondria.
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