The anti-vascular therapy has been extensively studied for high performance tumor therapy by suppressing the tumor angiogenesis or cutting off the existing tumor vasculature. We have previously reported a novel anti-t...The anti-vascular therapy has been extensively studied for high performance tumor therapy by suppressing the tumor angiogenesis or cutting off the existing tumor vasculature. We have previously reported a novel anti-tumor treatment technique using radiofrequency （RF）-assisted ga- dofullerene nanocrystals （GFNCs） to selectively disrupt the tumor vasculature. In this work, we further revealed the changes on morphology and functionality of the tumor vas-culature during the high-performance RF-assisted GFNCs treatment in vivo. Here, a dearly evident mechanism of this technique in tumor vascular disruption was elucidated. Based on the H22 tumor bearing mice with dorsal skin flap chamber （DSFC） mode] and the dynamic contrast enhanced magnetic resonance imaging （DCE-MRI） technique, it was revealed that the GFNCs would selectively inset in the gaps of tumor vas-culature due to the innately incomplete structures and unique microenvironment of tumor vasculature,＇ and they damaged the surrounding endothelia cells excited by the RF to induce a phase transition accompanying with size expansion. Soon afterwards, the blood flow of the tumor blood vessels was permanently shut off, causing the entire tumor vascular net- work to collapse within 24 h after the treatment. The RF-as- sistant GFNCs technique was proved to aim at the tumor vasculatnre precisely, and was harmless to the normal vascu- lature. The current studies provide a rational explanation on the high efficiency anticancer activity of the RF-assisted GFNCs treatment, suggesting a novel technique with potent clinical application.展开更多
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 ...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.展开更多
基金supported by the National Natural Science Foundation of China(51472248 and 51502301)National Major Scientific Instruments and Equipments Development Project(ZDYZ2015-2)the Key Research Program of the Chinese Academy of Sciences(QYZDJ-SSW-SLH025)
文摘The anti-vascular therapy has been extensively studied for high performance tumor therapy by suppressing the tumor angiogenesis or cutting off the existing tumor vasculature. We have previously reported a novel anti-tumor treatment technique using radiofrequency （RF）-assisted ga- dofullerene nanocrystals （GFNCs） to selectively disrupt the tumor vasculature. In this work, we further revealed the changes on morphology and functionality of the tumor vas-culature during the high-performance RF-assisted GFNCs treatment in vivo. Here, a dearly evident mechanism of this technique in tumor vascular disruption was elucidated. Based on the H22 tumor bearing mice with dorsal skin flap chamber （DSFC） mode] and the dynamic contrast enhanced magnetic resonance imaging （DCE-MRI） technique, it was revealed that the GFNCs would selectively inset in the gaps of tumor vas-culature due to the innately incomplete structures and unique microenvironment of tumor vasculature,＇ and they damaged the surrounding endothelia cells excited by the RF to induce a phase transition accompanying with size expansion. Soon afterwards, the blood flow of the tumor blood vessels was permanently shut off, causing the entire tumor vascular net- work to collapse within 24 h after the treatment. The RF-as- sistant GFNCs technique was proved to aim at the tumor vasculatnre precisely, and was harmless to the normal vascu- lature. The current studies provide a rational explanation on the high efficiency anticancer activity of the RF-assisted GFNCs treatment, suggesting a novel technique with potent clinical application.
基金supported by the National Natural Science Foundation of China(51472248,11179006 and 51372251)the Key Research Program of the Chinese Academy of Sciences(KGZDEW-T02 and XDA09030302)
文摘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.
