Sonodynamic Therapeutic Effects of Sonosensitizers with Different Intracellular Distribution Delivered by Hollow Nanocapsules Exhibiting Cytosol Specific Release.
Ryoma TeranishiTakayuki MatsudaEiji YubaKenji KonoAtsushi HaradaPublished in: Macromolecular bioscience (2019)
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.
Keyphrases
- reactive oxygen species
- cancer therapy
- cell death
- cell cycle arrest
- drug delivery
- magnetic resonance imaging
- induced apoptosis
- single cell
- emergency department
- pi k akt
- bone marrow
- endoplasmic reticulum stress
- computed tomography
- mesenchymal stem cells
- adverse drug
- endoplasmic reticulum
- mass spectrometry
- smoking cessation
- replacement therapy