A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

Abstract

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.

Real-time monitoring of tumor vascular disruption induced by radiofrequency assisted gadofullerene

“…S3). Accordingly, the tissue pathological analysis in the previous report exhibited that the RF assisted GFNCs displayed negligible damage to the normal tissues, even to the liver tissue with higher accumulation of GFNCs [22].…”

“…Recently, we reported a new technique based on the radiofrequency (RF)-assisted gadofullerene nanocrystals (GFNCs) which exhibited high-efficient antitumor activity and low toxicity to normal tissues, and may overcome the big problems of VDAs [22]. Briefly, the gadofullerene based nanomaterials were modified with hydroxyl groups on the surface of carbon cage to form the water soluble GFNCs [23,24].…”

“…When performing the tumor therapy, the GFNCs solution was intravenously injected to the testing tumor-bearing mice, and partial of the GFNCs particles would reach the tumor blood vessels along with the blood flow and try to penetrate out through the vascular leaks. With the radiation by RF, the tumor vasculature was speculated to be destroyed with the explosive volume expansion of GFNCs in anti-tumor activity but not the magnetocaloric effect [22]. On the contrast, for the vasculature of normal organs, there are no leaks on the blood vessel walls to trap the GFNCs particles, so the phase transition of GFNCs would be harmless.…”

Curcumin-encapsulated polymeric nanoparticles for metastatic osteosarcoma cells treatment

“…2b). It is well known that nanoparticles with radius less than 100 nm could target passively to solid tumor by the enhanced permeability and retention (EPR) effect [47][48][49]. The Cur-NPs satisfy the above conditions, and therefore have the po- tential for the application in cancer therapy.…”

A novel bone marrow targeted gadofullerene agent protect against oxidative injury in chemotherapy

“…Of them we have special interests on fullerenes and metallofullerenes due to their low toxic [28][29][30] metabolizable properties in vivo [31][32][33], as well as their excellent radical scavenging properties. In fact, fullerenes have been reported to protect cells from both ROS hurt and regulate apoptotic process in different biological model systems [34][35][36][37][38], e.g., Moussa et al [39] recently reported that oral administration of C 60 dissolved in olive oil could reduce the oxidative stress induced by the CCl 4 intoxication and largely prolong the lifespan of test rats to double.…”