Reactive oxygen species (ROS) and glutathione (GSH) dual responsive nanoparticulate drug delivery systems (nano-DDSs) hold great promise to improve the therapeutic efficacy and alleviate the side effects of chemo drugs in cancer theranosis. Herein, hydrogen peroxide (HO) and GSH dual responsive thioketal nanoparticle (TKN) was rationally designed for paclitaxel (PTX) delivery. Compared to other stimuli-sensitive nano-DDSs, this dual responsive DDS is not only sensitive to biologically relevant HO and GSH for on-demand drug release but also biodegradable into biocompatible byproducts after fulfilling its delivering task. Considering the heterogeneous redox potential gradient, the PTX loaded TKNs (PTX-TKNs) might first respond to the extracellular ROS and then to the intracellular GSH, achieving a programmable release of PTX at the tumor site. The selective toxicity of PTX-TKNs to tumor cells with high levels of ROS and GSH was verified both in vitro and in vivo.
It has long been a dream to achieve tumor targeting therapy that can efficiently reduce the toxicity and severe side effects of conventional antitumor chemotherapeutic agents. Taking advantage of the abnormalities of tumor vasculature, we demonstrate here a new powerful tumor vascular-targeting therapeutic technique for solid cancers that applies advanced nanotechnology to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels. Water soluble magnetic Gd@C82 nanocrystals of the chosen sizes are deliberately designed with abilities to penetrate into the leaky tumor blood vessels. By triggering the radiofrequency induced phase transition of gadofullerene nanocrystals while extravasating the tumor blood vessel, the explosive structural change of nanoparticles generates a devastating impact on abnormal tumor blood vessels, resulting in a rapid and extensive ischemia necrosis and shrinkage of the tumors. This unprecedented target-specific physiotherapy is found to work perfectly for advanced and refractory solid tumors.
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