635 replies to this topic

[Kalliste]

Some are trying to conjugate fullerenes with other phytochemical compounds for cancer therapy.

 

 

Abstract: One important strategy to develop effective anticancer agents is based on natural products. Many active phytochemicals are in human clinical trials and have been used for a long time, alone and in association with conventional anticancer drugs, for the treatment of various types of cancers. A great number of in vitro, in vivo and clinical reports document the multi-target anticancer activities of isothiocyanates and of compounds characterized by a naphthalenetetracarboxylic diimide scaffold. In order to search for new anticancer agents with a better pharmaco-toxicological profile, we investigated hybrid compounds obtained by inserting isothiocyanate group(s) on a naphthalenetetracarboxylic diimide scaffold. Moreover, since water-soluble fullerene derivatives can cross cell membranes thus favoring the delivery of anticancer therapeutics, we explored the cytostatic and cytotoxic activity of hybrid compounds conjugated with fullerene. We studied their cytostatic and cytotoxic effects on a human T-lymphoblastoid cell line by using different flow cytometric assays. In order to better understand their pharmaco-toxicological potential, we also analyzed their genotoxicity. Our global results show that the synthesized compounds reduced significantly the viability of leukemia cells. However, the conjugation with a non-toxic vector did not increase their anticancer potential. This opens an interesting research pattern for certain fullerene properties.

http://www.mdpi.com/2072-6651/7/2/535

[Kalliste]

 

Multi-endpoint, High-Throughput Study of Nanomaterial Toxicity in Caenorhabditis elegans

The booming nanotechnology industry has raised public concerns about the environmental health and safety impact of engineered nanomaterials (ENMs). High-throughput assays are needed to obtain toxicity data for the rapidly increasing number of ENMs. Here we present a suite of high-throughput methods to study nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the population level, our system measures food consumption of thousands of animals to evaluate population fitness. At the organism level, our automated system analyzes hundreds of individual animals for body length, locomotion speed, and lifespan. To demonstrate the utility of our system, we applied this technology to test the toxicity of 20 nanomaterials at four concentrations. Only fullerene nanoparticles (nC₆₀), fullerol, TiO₂, and CeO₂ showed little or no toxicity. Various degrees of toxicity were detected from different forms of carbon nanotubes, graphene, carbon black, Ag, and fumed SiO₂ nanoparticles. Aminofullerene and ultraviolet-irradiated nC₆₀ also showed small but significant toxicity. We further investigated the effects of nanomaterial size, shape, surface chemistry, and exposure conditions on toxicity. Our data are publicly available at the open-access nanotoxicity database www.QuantWorm.org/nano.

http://pubs.acs.org/....1021/es5056462

http://www.frogheart...c-60-fullerenes

Edited by Cosmicalstorm, 02 March 2015 - 08:48 PM.

[Kalliste]

Here is a short primer on what is known in general about C60. Useful for those who are new to C60 molecules.

http://www.ias.ac.in...2/0123-0135.pdf

[Kalliste]

Fullerenes used to remove metals from water. We know the body can remove aggregates of C60, so maybe C60-oo binds to metals and allows the body to remove them? Too far fetched perhaps.

 

 

Treated Buckyballs Can Remove Toxic Metal Particles from Liquids

Published on February 11, 2015 at 6:14 AM

Treated buckyballs not only remove valuable but potentially toxic metal particles from water and other liquids, but also reserve them for future use, according to scientists at Rice University.

 

The Rice lab of chemist Andrew Barron has discovered that carbon-60 fullerenes (aka buckyballs) that have gone through the chemical process known as hydroxylation aggregate into pearl-like strings as they bind to and separate metals – some better than others – from solutions. Potential uses of the process include the environmentally friendly removal of metals from acid mining drainage fluids, a waste product of the coal industry, as well as from fluids used for hydraulic fracturing in oil and gas production.

Barron said the treated buckyballs handled metals with different charges in unexpected ways, which may make it possible to pull specific metals from complex fluids while ignoring others.

The study led by Rice undergraduate Jessica Heimann appeared in the Royal Society of Chemistry journal Dalton Transactions.

Previous research in Barron’s lab had shown that hydroxylated fullerenes (known as fullerenols) combined with iron ions to form an insoluble polymer. Heimann and colleagues conducted a series of experiments to explore the relative binding ability of fullerenols to a range of metals.

“It’s all very well to say I can take metals out of water, but for more complex fluids, the problem is to take out the ones you actually want,” Barron said. “Acid mining waste, for example, has large amounts of iron and aluminum and small amounts of nickel and zinc and copper, the ones you want. To be frank, iron and aluminum are not the worst metals to have in your water, because they’re in natural water, anyway.

“So our goal was to see if there is a preference between different types of metal, and we found one. Then the question was: Why?”

The answer was in the ions. An atom or molecule with more or fewer electrons than protons is an ion, with a positive or negative charge. All the metals the Rice lab tested were positive, with either 2-plus or 3-plus charges.

“Normally, the bigger the metal, the better it separates,” Barron said, but experiments proved otherwise. Two-plus metals with a smaller ionic radius bound better than larger ones. (Of those, zinc bound most tightly.) But for 3-plus ions, large worked better than small.

“That’s really weird,” Barron said. “The fact that there are diametrically opposite trends for metals with a 2-plus charge and metals with a 3-plus charge makes this interesting. The result is we should be able to preferentially separate out the metals we want.”

The experiments found that fullerenols combined with a dozen metals, turning them into solid cross-linked polymers. In order of effectiveness and starting with the best, the metals were zinc, cobalt, manganese, nickel, lanthanum, neodymium, cadmium, copper, silver, calcium, iron and aluminum.

The “pearl” reference isn’t far from literal, as one inspiration for the paper was the fact that metal ions are cross-linking agents for proteins that give certain marine mussels an amazing ability to adhere to wet rocks.

Heimann, a senior, started on the project before spending a semester at Rice’s sister institution in Germany, Jacobs University. “I initially worked with carbon nanotubes, oxidizing them to see how they would bind metals, and then I went abroad,” she said. By the time she came back, Barron was ready to try C-60. “Coming from Rice and its history with buckyballs, I thought that would be really cool,” Heimann said.

“I liked being able to see the end goal of making a filter that could be used to address contaminated water,” she said.

Barron said fullerenols act as chelate agents, which determine how ions and molecules bind with metal ions. Experiments with various metals showed the fullerenols bound with them in less than a minute, after which the combined solids could be filtered out.

Barron said the choices of aluminum, zinc and nickel for testing were due to their co-presence with iron in acid mining drainage water. Similarly, cadmium was tested for its association with fertilizer and sewage sludge and copper with mining discharge. Nickel, lanthanum and neodymium are used in batteries and drive motors in hybrid vehicles.

Barron said the research shows the versatility of the buckyball, discovered at Rice in 1985 by Nobel Prize winners Rick Smalley, Robert Curl and Harold Kroto. It also points the way forward. “The understanding we now have is allowing us to find alternatives to C-60s to design ways in which we can separate out metals more efficiently,” he said.

Co-authors of the paper are Rice graduate student Lauren Morrow and alumnus Robin Anderson. Barron is the Charles W. Duncan Jr.-Welch Professor of Chemistry and a professor of materials science and nanoengineering.

http://www.azonano.c...px?newsID=32058

[niner]

Fullerenes used to remove metals from water. We know the body can remove aggregates of C60, so maybe C60-oo binds to metals and allows the body to remove them? Too far fetched perhaps.

 

Yeah, probably not an effect of c60oo.  In this report, they used fullerols, which are polyhydroxylated.  The most common one is C60(OH)22, which is a lot of hydroxyls.  Two hydroxyls side by side can chelate a metal.  It's kind of a cool result that they formed long chains of -fullerol-metal-fullerol-metal-.  C60oo has no hydroxyls on it that I know of, and also has a fatty acid chain that might get in the way.  C60oo could possibly get hydroxylated over time while in the body, as it soaks up hydroxyl radicals.  The metals that I would most like to be rid of had the least affinity for fullerol, and the highest was zinc, so it's probably not a thing you'd want to use as a therapy.

[sensei]

 

Fullerenes used to remove metals from water. We know the body can remove aggregates of C60, so maybe C60-oo binds to metals and allows the body to remove them? Too far fetched perhaps.

 

Yeah, probably not an effect of c60oo.  In this report, they used fullerols, which are polyhydroxylated.  The most common one is C60(OH)22, which is a lot of hydroxyls.  Two hydroxyls side by side can chelate a metal.  It's kind of a cool result that they formed long chains of -fullerol-metal-fullerol-metal-.  C60oo has no hydroxyls on it that I know of, and also has a fatty acid chain that might get in the way.  C60oo could possibly get hydroxylated over time while in the body, as it soaks up hydroxyl radicals.  The metals that I would most like to be rid of had the least affinity for fullerol, and the highest was zinc, so it's probably not a thing you'd want to use as a therapy.

 

 

Ascorbate (Vitamin C) is an exceptional chelator of metals

 

"Although nuclear bound Al(III) was found to be highly refractory to removal, the combination of AS+FG was found to be particularly effective in removing Al(III) from the nuclear matrix."

 

http://www.ncbi.nlm....pubmed/15206824

 

There is some data that shows a short term pro-oxidant effect of Sodium Ascorbate  when used in conjunction with  EDTA.  Apparently due to reduction of glutathione peroxidase and SOD

 

http://www.ncbi.nlm....pubmed/15917185

 

 

 -- perhaps adding C60OO + Sodium Ascorbate + EDTA is the best combination -- with the C60 ameliorating the short term pro-oxidant effects of the Sodium Ascorbate.

[pone11]

Fullerenes used to remove metals from water. We know the body can remove aggregates of C60, so maybe C60-oo binds to metals and allows the body to remove them? Too far fetched perhaps.

 

 

Treated Buckyballs Can Remove Toxic Metal Particles from Liquids

Published on February 11, 2015 at 6:14 AM

Treated buckyballs not only remove valuable but potentially toxic metal particles from water and other liquids, but also reserve them for future use, according to scientists at Rice University.

 

The Rice lab of chemist Andrew Barron has discovered that carbon-60 fullerenes (aka buckyballs) that have gone through the chemical process known as hydroxylation aggregate into pearl-like strings as they bind to and separate metals – some better than others – from solutions. Potential uses of the process include the environmentally friendly removal of metals from acid mining drainage fluids, a waste product of the coal industry, as well as from fluids used for hydraulic fracturing in oil and gas production.

Barron said the treated buckyballs handled metals with different charges in unexpected ways, which may make it possible to pull specific metals from complex fluids while ignoring others.

The study led by Rice undergraduate Jessica Heimann appeared in the Royal Society of Chemistry journal Dalton Transactions.

Previous research in Barron’s lab had shown that hydroxylated fullerenes (known as fullerenols) combined with iron ions to form an insoluble polymer. Heimann and colleagues conducted a series of experiments to explore the relative binding ability of fullerenols to a range of metals.

“It’s all very well to say I can take metals out of water, but for more complex fluids, the problem is to take out the ones you actually want,” Barron said. “Acid mining waste, for example, has large amounts of iron and aluminum and small amounts of nickel and zinc and copper, the ones you want. To be frank, iron and aluminum are not the worst metals to have in your water, because they’re in natural water, anyway.

“So our goal was to see if there is a preference between different types of metal, and we found one. Then the question was: Why?”

The answer was in the ions. An atom or molecule with more or fewer electrons than protons is an ion, with a positive or negative charge. All the metals the Rice lab tested were positive, with either 2-plus or 3-plus charges.

“Normally, the bigger the metal, the better it separates,” Barron said, but experiments proved otherwise. Two-plus metals with a smaller ionic radius bound better than larger ones. (Of those, zinc bound most tightly.) But for 3-plus ions, large worked better than small.

“That’s really weird,” Barron said. “The fact that there are diametrically opposite trends for metals with a 2-plus charge and metals with a 3-plus charge makes this interesting. The result is we should be able to preferentially separate out the metals we want.”

The experiments found that fullerenols combined with a dozen metals, turning them into solid cross-linked polymers. In order of effectiveness and starting with the best, the metals were zinc, cobalt, manganese, nickel, lanthanum, neodymium, cadmium, copper, silver, calcium, iron and aluminum.

The “pearl” reference isn’t far from literal, as one inspiration for the paper was the fact that metal ions are cross-linking agents for proteins that give certain marine mussels an amazing ability to adhere to wet rocks.

Heimann, a senior, started on the project before spending a semester at Rice’s sister institution in Germany, Jacobs University. “I initially worked with carbon nanotubes, oxidizing them to see how they would bind metals, and then I went abroad,” she said. By the time she came back, Barron was ready to try C-60. “Coming from Rice and its history with buckyballs, I thought that would be really cool,” Heimann said.

“I liked being able to see the end goal of making a filter that could be used to address contaminated water,” she said.

Barron said fullerenols act as chelate agents, which determine how ions and molecules bind with metal ions. Experiments with various metals showed the fullerenols bound with them in less than a minute, after which the combined solids could be filtered out.

Barron said the choices of aluminum, zinc and nickel for testing were due to their co-presence with iron in acid mining drainage water. Similarly, cadmium was tested for its association with fertilizer and sewage sludge and copper with mining discharge. Nickel, lanthanum and neodymium are used in batteries and drive motors in hybrid vehicles.

Barron said the research shows the versatility of the buckyball, discovered at Rice in 1985 by Nobel Prize winners Rick Smalley, Robert Curl and Harold Kroto. It also points the way forward. “The understanding we now have is allowing us to find alternatives to C-60s to design ways in which we can separate out metals more efficiently,” he said.

Co-authors of the paper are Rice graduate student Lauren Morrow and alumnus Robin Anderson. Barron is the Charles W. Duncan Jr.-Welch Professor of Chemistry and a professor of materials science and nanoengineering.

http://www.azonano.c...px?newsID=32058

 

This is actually what concerns me about C60.   People want to believe it only collects "bad" things like superoxide and hydroxyl radicals.   What if it also collects "good" things like essential minerals zinc, copper, etc.    From the study you linked:

 

"The experiments found that fullerenols combined with a dozen metals, turning them into solid cross-linked polymers. In order of effectiveness and starting with the best, the metals were zinc, cobalt, manganese, nickel, lanthanum, neodymium, cadmium, copper, silver, calcium, iron and aluminum."

 

Some of those are bad for the body and others are essential nutrients that you may or may not have in deficient amounts already.

 

So you might start out on C60 and get the squelching of free radicals benefit immediately, and feel great.  Then as tissue saturation (with a long half life of polyfats in cell membranes) increases, the C60 may start to deplete you of essential nutrients.   You therefore feel great at first, and then slowly over time create potentially very dangerous mineral imbalances or shortages.   I think it requires very careful monitoring, particularly of your RBC levels - not just your serum levels - starting with a baseline before you take C60, and then monitoring every few months thereafter to see if any of those levels start to trend down.

 

I have a thread here on Longecity where I supplied studies about copper.  Copper is one of those minerals that has a very narrow range of benefit.   It has real toxicity at high levels, but at low levels you get horrific cardiac events like arterial rupture.   So you never want to go too low on copper.  You won't get any warning in symptoms either as that happens.   The kind of negative events that take place on low copper are sudden, without warning, and often fatal events.   That's just one example.

 

There really should be some safety studies done on high dose C60 in primates where they can get meaningful metabolite measurements over a five year period, as the tissue saturation slowly increases.

 

I understand that the linked study did not use C60.   See next post on hydroxylation of C60.

Edited by pone11, 03 March 2015 - 08:45 PM.

[pone11]

 

Fullerenes used to remove metals from water. We know the body can remove aggregates of C60, so maybe C60-oo binds to metals and allows the body to remove them? Too far fetched perhaps.

 

Yeah, probably not an effect of c60oo.  In this report, they used fullerols, which are polyhydroxylated.  The most common one is C60(OH)22, which is a lot of hydroxyls.  Two hydroxyls side by side can chelate a metal.  It's kind of a cool result that they formed long chains of -fullerol-metal-fullerol-metal-.  C60oo has no hydroxyls on it that I know of, and also has a fatty acid chain that might get in the way.  C60oo could possibly get hydroxylated over time while in the body, as it soaks up hydroxyl radicals.  The metals that I would most like to be rid of had the least affinity for fullerol, and the highest was zinc, so it's probably not a thing you'd want to use as a therapy.

 

 

That's comforting, but as you state - and summarized nicely a few days ago - C60 might soak up hydroxyls and become hydroxylated over time.   So C60 itself might be relatively risk free to attract essential minerals, but a hydroxylated C60 that is stuck in lipid membranes for a long period of time might be a problem.   And given that the complexes of the electron transport chain use bound metals like iron-sulfate complexes, copper, etc, it does give you some pause.    At least there should be a primate safety study that gives high dose C60 for a minimum of five years to assess affects on mineral balances in deep tissues.   Lacking that safety research, humans who are taking C60 are basically becoming the alpha testers for that.

[caliban]

Some posts have been deleted. Reminder of thread rules in the 1st entry and post #376.

 

 

[Turnbuckle]

 C60oo has no hydroxyls on it that I know of, and also has a fatty acid chain that might get in the way.  C60oo could possibly get hydroxylated over time while in the body, as it soaks up hydroxyl radicals. 

 

Likely it does, as it appears that adding OH groups is fairly easy, just requiring H2O2 and time. 

 

2.2 Highly polyhydroxylated fullerenols

 

To avoid contamination by Na+ ions, we examined the use of hydrogen peroxide (H2O2) as a hydroxylation reagent instead of NaOH. Thus, we have found a new and facile approach for synthesizing high-degree fullerenols that have high water solubility without using any Na salts (Kokubo et al., 2008). The reddish brown suspension of fullerenol C60(OH)12 in 30% aqueous H2O2 was stirred vigorously at 60 °C under air until it turned to a transparent yellow solution, which occurred within 2–4 days (Scheme 2a). To this solution, a mixture of 2-propanol, diethyl ether, and hexane as an antisolvent was added to afford a yellowish brown to milky white precipitation of the desirable high-degree fullerenol C60(OH)36· 8H2O. A longer reaction time of up to two weeks gave the similar but more water-soluble fullerenol C60(OH)40· 9H2O. 

 

This new approach using H2O2 to synthesize high-degree fullerenols was useful; however, the starting material was limited to C60(OH)12 and was not applicable to pristine C60. We then improved the method in order to provide a facile, one-step method for synthesizing fullerenol from pristine C60; we added an NH3 aqueous solution to the H2O2 aqueous solution to give similar water-soluble fullerenols, although they contained some undesirable nitrogen-containing groups, along with hydroxyl groups (Matsubayashi et al., 2009). We further improved the method, synthesizing pure C60(OH)44· 8H2O fullerenol with no nitrogen in one step from pristine C60. To the best of our knowledge, this fullerenol has the largest number of hydroxyl groups per C60 among the fullerenols reported so far; this fullerenol was obtained by a two-phase synthesis in the presence of tetrabutylammonium hydroxide (TBAH) as a phase transfer catalyst (PTC) (Scheme 2b) (Kokubo et al., 2010). The fullerenol exhibits a very high water solubility of up to 64.9 mg/mL.  

 

http://cdn.intechope...fs-wm/36889.pdf

 

 

 

This process is slow, however, and C60 will likely be gone from the mitochondria before it becomes significant.

[pone11]

 

This process is slow, however, and C60 will likely be gone from the mitochondria before it becomes significant.

 

 

That's the million dollar question:  how soon does C60 leave mitochondria?   We know it leaves serum quickly, but if it gets bound into lipid structure in the mitochondrial membrane that have long half-lives, will C60 remain around for the duration of the lipid's life?

[Turnbuckle]

 

 

This process is slow, however, and C60 will likely be gone from the mitochondria before it becomes significant.

 

 

That's the million dollar question:  how soon does C60 leave mitochondria?   We know it leaves serum quickly, but if it gets bound into lipid structure in the mitochondrial membrane that have long half-lives, will C60 remain around for the duration of the lipid's life?

 

 

From experiments with C70 (which unlike C60, localizes more to the ER), it appears that it is still detectable in mitochondria at one week, but seems more concentrated. See figures 2-5.

 

http://www.ncbi.nlm....les/PMC2888797/

[pone11]

 

 

 

This process is slow, however, and C60 will likely be gone from the mitochondria before it becomes significant.

 

 

That's the million dollar question:  how soon does C60 leave mitochondria?   We know it leaves serum quickly, but if it gets bound into lipid structure in the mitochondrial membrane that have long half-lives, will C60 remain around for the duration of the lipid's life?

 

 

From experiments with C70 (which unlike C60, localizes more to the ER), it appears that it is still detectable in mitochondria at one week, but seems more concentrated. See figures 2-5.

 

http://www.ncbi.nlm....les/PMC2888797/

 

 

It would be nice to see someone do a study on human cells where they track the full amount of time from introduction of C60 to the point where 99% of it is out of the cell.     

 

I think the study you posted is more about where C70 vs C60 gets absorbed, and not so much about how much escapes and how quickly.

[mikela]

Not sure if this is relevant but thought some of the experts might want to comment:

 

http://www.science20...er_cells-153658

[Kalliste]

Bolded some interesting parts. Again, not sure how this exactly relates to our beloved Lipofullerenes but it's nice to see that it's not wreaking molecular havoc.

 

 

https://ecs.confex.c...Paper50636.html

Electrical-field cancer therapy (EFCT) is a non-invasive means of inducing tumor necrosis by exposing cancer to electric fields (EFs) at a multitude of frequencies (10 Hz – 200 MHz). Clinical cancer trials have shown that safe levels of amplitude-modulated (AM) EFs (0.1 Hz-114 kHz) administered via an intrabuccal tongue-shaped probe elicit therapeutic responses^{1, 2}. Separate clinical studies have also shown therapeutic benefits through the use of insulated electrodes powered at higher frequencies of 100-300 kHz^3-6. Although EFs have been shown to cause thermal and non-thermal cancer destruction, their mechanisms are poorly investigated and still not fully understood^1-6. Furthermore, EFs can enhance the efficacy of chemotherapy drugs at dosages far less than is currently used in the clinic. However, there are still critical barriers that are impeding the use of this technology in an FDA-approved clinical setting. Namely; (i) the ability to image and predict the heating effects of EF exposure upon internal organs, tissues, and tumors; and (ii) a method to optimize and target EF-induced thermal and non-thermal anti-cancer effects to reduce neighboring healthy cell toxicity.

We have published on the ability of highly water soluble C₆₀-serinol (C₆₀-ser) to be used as a transfection agent⁷ and the molecule’s ability to non-covalently internalize within a melanoma antibody in significant quantities without significantly affecting antibody-antigen binding⁸. These abilities are second to the molecule’s non-toxicity. We have also developed a C₆₀-ser conjugate with a fluorescent label (PF-633) for intracellular tracking. This complex directly competes with unlabeled C₆₀-ser without altering biological behavior⁹. Tracking the fluorescence we discovered C₆₀-serPF can cross both cellular and nuclear membranes without producing any damage to the cell. Furthermore, C₆₀-serPF internalizes within living cells in association with serum proteins through multiple energy-dependent pathways (not passive internalization).

In a mouse model of liver cancer, the C₆₀-serPF conjugate is detected in most tissues, permeating through the altered vasculature of the tumor and the tightly-regulated blood brain barrier while evading the reticulo-endothelial system. These findings suggest C₆₀-ser can serve as a potential delivery vehicle for therapeutic agents with intranuclear activity (DNA plasmids, drugs such as paclitaxel, gemcitabine, camptothecin, cisplatin, siRNA, transcription factors, epigenetic agents, etc.) to treat cancer. Targeted delivery of these vehicles can be achieved by their binding with tumor-specific antibodies, due to the known affinity of water-soluble fullerenes for antibodies to form immunoconjugates.

In this study, we have investigated the interactions of variable frequency EFs (10 HZ – 250 MHz) with various C₆₀ derivatives (Figure 1) as a means of enhancing the efficacy of EFCT. We report on the enhanced toxicity of C₆₀-Gemcitabine/Paclitaxel/Camptothecin conjugates, when used in conjunction with EFCT, as well as the intracellular distribution of fluorescently tagged (PF-633) C₆₀-ser, as a function of EF exposure.

 

 

[Kalliste]

Another C60 version wrapped up in some lipids and a bunch of other things, the abstract says nothing about any toxicity which is always nice.

 

 

Nanoscale. 2015 Mar 12;7(12):5411-26. doi: 10.1039/c4nr04257c.

Multi-functional liposomes showing radiofrequency-triggered release and magnetic resonance imaging for tumor multi-mechanism therapy.

Du B¹, Han S, Li H, Zhao F, Su X, Cao X, Zhang Z.

Author information

Abstract

Recently, nanoplatforms with multiple functions, such as tumor-targeting drug carriers, MRI, optical imaging, thermal therapy etc., have become popular in the field of cancer research. The present study reports a novel multi-functional liposome for cancer theranostics. A dual targeted drug delivery with radiofrequency-triggered drug release and imaging based on the magnetic field influence was used advantageously for tumor multi-mechanism therapy. In this system, the surface of fullerene (C60) was decorated with iron oxide nanoparticles, and PEGylation formed a hybrid nanosystem (C60-Fe3O4-PEG2000). Thermosensitive liposomes (dipalmitoylphosphatidylcholine, DPPC) with DSPE-PEG2000-folate wrapped up the hybrid nanosystem and docetaxel (DTX), which were designed to combine features of biological and physical (magnetic) drug targeting for fullerene radiofrequency-triggered drug release. The magnetic liposomes not only served as powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agents, but also as powerful agents for photothermal ablation of tumors. Furthermore, a remarkable thermal therapy combined chemotherapy multi-functional liposome nanoplatform converted radiofrequency energy into thermal energy to release drugs from thermosensitive liposomes, which was also observed during both in vitro and in vivo treatment. The multi-functional liposomes also could selectively kill cancer cells in highly localized regions via their excellent active tumor targeting and magnetic targeted abilities.

http://pubs.rsc.org/...7C#!divAbstract

[Kalliste]

Distribution of C14 labeled C60 in mice and rats.

 

 

Abstract

A comprehensive distribution study was conducted in female rats and mice exposed to a suspension of uniformly carbon-14-labeled C₆₀ ([¹⁴C(U)]C₆₀). Rodents were administered [¹⁴C(U)]C₆₀ (~0.9 mg kg⁻¹ body weight) or 5% polyvinylpyrrolidone-saline vehicle alone via a single tail vein injection. Tissues were collected at 1 h and 1, 7, 14 and 30 days after administration. A separate group of rodents received five daily injections of suspensions of either [¹⁴C(U)]C₆₀ or vehicle with tissue collection 14 days post exposure. Radioactivity was detected in over 20 tissues at all time points. The highest concentration of radioactivity in rodents at each time point was in liver, lungs and spleen. Elimination of [¹⁴C(U)]C₆₀ was < 2% in urine and feces at any 24 h time points. [¹⁴C(U)]C₆₀ and [¹⁴C(U)]C₆₀-retinol were detected in liver of rats and together accounted for ~99% and ~56% of the total recovered at 1 and 30 days postexposure, respectively. The blood radioactivity at 1 h after [¹⁴C(U)]C₆₀ exposure was fourfold higher in rats than in mice; blood radioactivity was still in circulation at 30 days post [¹⁴C(U)]C₆₀ exposure in both species (<1%). Levels of oxidative stress markers increased by 5 days after exposure and remained elevated, while levels of inflammation markers initially increased and then returned to control values. The level of cardiovascular marker von Willebrand factor, increased in rats, but remained at control levels in mice. This study demonstrates that [¹⁴C(U)]C₆₀ is retained in female rodents with little elimination by 30 days after i.v. exposure, and leads to systemic oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.

http://onlinelibrary...3110/references

[pone11]

Distribution of C14 labeled C60 in mice and rats.

 

 

Abstract

A comprehensive distribution study was conducted in female rats and mice exposed to a suspension of uniformly carbon-14-labeled C₆₀ ([¹⁴C(U)]C₆₀). Rodents were administered [¹⁴C(U)]C₆₀ (~0.9 mg kg⁻¹ body weight) or 5% polyvinylpyrrolidone-saline vehicle alone via a single tail vein injection. Tissues were collected at 1 h and 1, 7, 14 and 30 days after administration. A separate group of rodents received five daily injections of suspensions of either [¹⁴C(U)]C₆₀ or vehicle with tissue collection 14 days post exposure. Radioactivity was detected in over 20 tissues at all time points. The highest concentration of radioactivity in rodents at each time point was in liver, lungs and spleen. Elimination of [¹⁴C(U)]C₆₀ was < 2% in urine and feces at any 24 h time points. [¹⁴C(U)]C₆₀ and [¹⁴C(U)]C₆₀-retinol were detected in liver of rats and together accounted for ~99% and ~56% of the total recovered at 1 and 30 days postexposure, respectively. The blood radioactivity at 1 h after [¹⁴C(U)]C₆₀ exposure was fourfold higher in rats than in mice; blood radioactivity was still in circulation at 30 days post [¹⁴C(U)]C₆₀ exposure in both species (<1%). Levels of oxidative stress markers increased by 5 days after exposure and remained elevated, while levels of inflammation markers initially increased and then returned to control values. The level of cardiovascular marker von Willebrand factor, increased in rats, but remained at control levels in mice. This study demonstrates that [¹⁴C(U)]C₆₀ is retained in female rodents with little elimination by 30 days after i.v. exposure, and leads to systemic oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.

http://onlinelibrary...3110/references

 

Am I reading this correctly that after 30 days 44% of the C60 remained in the liver?  Why didn't they extend this study out to see how long it takes to get 95%+ out of the system?   What a wasted opportunity.

 

How do others explain this result that C60 increased markers of oxidative stress?

 

Does anyone have full text to this study?   Sci-hub has a paywall today.

Edited by pone11, 17 March 2015 - 07:17 PM.

[Nuke]

The problem I see is that this is not C60 as we use it.  They say it was in suspension in polyvinylpyrrolidone-saline, thus making it nC60. From other studies it does seem that nC60 can be problematic.

 

I would also like to see the full text.

[Invariant]

 

Distribution of C14 labeled C60 in mice and rats.

 

 

Abstract

A comprehensive distribution study was conducted in female rats and mice exposed to a suspension of uniformly carbon-14-labeled C₆₀ ([¹⁴C(U)]C₆₀). Rodents were administered [¹⁴C(U)]C₆₀ (~0.9 mg kg⁻¹ body weight) or 5% polyvinylpyrrolidone-saline vehicle alone via a single tail vein injection. Tissues were collected at 1 h and 1, 7, 14 and 30 days after administration. A separate group of rodents received five daily injections of suspensions of either [¹⁴C(U)]C₆₀ or vehicle with tissue collection 14 days post exposure. Radioactivity was detected in over 20 tissues at all time points. The highest concentration of radioactivity in rodents at each time point was in liver, lungs and spleen. Elimination of [¹⁴C(U)]C₆₀ was < 2% in urine and feces at any 24 h time points. [¹⁴C(U)]C₆₀ and [¹⁴C(U)]C₆₀-retinol were detected in liver of rats and together accounted for ~99% and ~56% of the total recovered at 1 and 30 days postexposure, respectively. The blood radioactivity at 1 h after [¹⁴C(U)]C₆₀ exposure was fourfold higher in rats than in mice; blood radioactivity was still in circulation at 30 days post [¹⁴C(U)]C₆₀ exposure in both species (<1%). Levels of oxidative stress markers increased by 5 days after exposure and remained elevated, while levels of inflammation markers initially increased and then returned to control values. The level of cardiovascular marker von Willebrand factor, increased in rats, but remained at control levels in mice. This study demonstrates that [¹⁴C(U)]C₆₀ is retained in female rodents with little elimination by 30 days after i.v. exposure, and leads to systemic oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.

http://onlinelibrary...3110/references

 

Am I reading this correctly that after 30 days 44% of the C60 remained in the liver?  Why didn't they extend this study out to see how long it takes to get 95%+ out of the system?   What a wasted opportunity.

 

How do others explain this result that C60 increased markers of oxidative stress?

 

Does anyone have full text to this study?   Sci-hub has a paywall today.

 

 

I think that's not what it says. It says that *of the labelled C60 that was recovered*, 56% was C60-retinol so 44% of the recovered C60 is in another form (most of it plain C60, and 1% in another form).

 

Could radioactive carbon cause an increase in oxidative stress at this dose?

 

I found the fulltext pdf here:

http://www.docdroid....cology.pdf.html

[pone11]

 

I think that's not what it says. It says that *of the labelled C60 that was recovered*, 56% was C60-retinol so 44% of the recovered C60 is in another form (most of it plain C60, and 1% in another form).

 

Could radioactive carbon cause an increase in oxidative stress at this dose?

 

I found the fulltext pdf here:

http://www.docdroid....cology.pdf.html

 

 

Thanks for correcting my misunderstanding.

 

The study asks great questions, and it has a wonderful setup to the experiment itself.   So why did they only test 30 days?   Frustrating.

 

I also wondered if the C14 could be causing the oxidative stress.   They should have created a control group with C60 only and looked for the same markers to compare across groups.   They address in the study to the right of Table 9 why they think the C14 generates too little radiation to have an effect, but I still think they should have had a control group with C60 only.

 

I am confused by Table 1 in the full text.  Why aren't they tracking the amount of C60 that left the body by urine or feces over the number of days they measure?   What's the point of just reporting concentrations in tissue if we do not know how much left the body at each of those measurement times?

Edited by pone11, 17 March 2015 - 10:24 PM.

[pone11]

Another thread was started regarding a new antioxidant named IAC.  Niner noticed in the results table of the full text that the researcher carefully dosed the animals at many different levels, and the results of this were dramatic.

 

I cannot get full text at the moment, but here is the study reference:

 

J Gerontol A Biol Sci Med Sci. 2014 Sep 4. pii: glu160. [Epub ahead of print]
Redox-Based Flagging of the Global Network of Oxidative Stress Greatly Promotes Longevity.

 

Niner felt that this antioxidant had a general structure that reminded him of C60, which is why I connect to this thread on C60.

 

Here is a post I made regarding the dosing issue:

http://www.longecity...ed/#entry719070

 

The point for C60 users to consider is that IAC resulted in 170% life extension only at a specific concentration.   Above this relatively mild concentration, it rapidly diminished its effect and started to reduce lifespan.   There was an extremely limited concentration where the antioxidant was effective, and a very broad spectrum where it was harmful.  If someone were self-dosing IAC without the benefit of research on dosing, they would almost surely under or over dose.

 

This is worth mentioning because no similar studies have been done with C60 yet.   And some of you are megadosing C60 on the assumption that more must be better.   This study on IAC is cautionary.

 

Edited by pone11, 17 March 2015 - 10:36 PM.

[Kalliste]

Some are trying to conjugate fullerenes with other phytochemical compounds for cancer therapy.

Abstract: One important strategy to develop effective anticancer agents is based on natural products. Many active phytochemicals are in human clinical trials and have been used for a long time, alone and in association with conventional anticancer drugs, for the treatment of various types of cancers. A great number of in vitro, in vivo and clinical reports document the multi-target anticancer activities of isothiocyanates and of compounds characterized by a naphthalenetetracarboxylic diimide scaffold. In order to search for new anticancer agents with a better pharmaco-toxicological profile, we investigated hybrid compounds obtained by inserting isothiocyanate group(s) on a naphthalenetetracarboxylic diimide scaffold. Moreover, since water-soluble fullerene derivatives can cross cell membranes thus favoring the delivery of anticancer therapeutics, we explored the cytostatic and cytotoxic activity of hybrid compounds conjugated with fullerene. We studied their cytostatic and cytotoxic effects on a human T-lymphoblastoid cell line by using different flow cytometric assays. In order to better understand their pharmaco-toxicological potential, we also analyzed their genotoxicity. Our global results show that the synthesized compounds reduced significantly the viability of leukemia cells. However, the conjugation with a non-toxic vector did not increase their anticancer potential. This opens an interesting research pattern for certain fullerene properties.

http://www.mdpi.com/2072-6651/7/2/535

Putting this find with the one saying olive oil kills cancer cells is interesting. I like the thought that we have found a way to craft a harmless anti cancer medicine by binding fullerenes to oo lipids.

Edited by Cosmicalstorm, 20 March 2015 - 11:37 AM.

[Kalliste]

This is C82. Tantalizing but not C60. Is this off-topic? I don't want to crash this thread. Seems very related.

 

 

Abstract

This article summarizes the overall issues surrounding cancer for the general audience. Individual differences between patients include genetic and non-genetic differences manifested in various cellular pathways, tumor heterogeneity and variability, differing contribution of tumor microenvironment and potential toward metastasis. Successful treatment of individuals depends on correctly interpreting all these factors and appropriately addressing the actual features by using customized therapy strategies, simultaneously or sequentially. Currently used chemotherapy agents are cytotoxic and typically target one of the major pathways; therefore they have to be applied in combination regimes. Nanomedicines however, have the potential advantage that more than one feature can be built into a complex nanodevice. This yet untapped potential is illustrated on the example of a gadolinium fullerenol cage molecule. Gd@C₈₂(OH)₂₂ has low toxicity, influences several biologic features simultaneously, displays tumoristatic properties, and is effective against triple-negative breast cancer cells. A deeper understanding of the exact relations between the physicochemical characteristics of this system and the biologic events may lead to a new class of efficient anticancer pharmaceutics.

 

[Kalliste]

 

Buckybomb: Reactive Molecular Dynamics Simulation

Vitaly V. Chaban ^*†‡, Eudes Eterno Fileti ^*‡, and Oleg V. Prezhdo ^*‡

^† Instituto de Ciência e Tecnologia, Universidade Federal de São Paulo, 12231-280 São José dos Campos, São Paulo, Brazil

^‡ Department of Chemistry, University of Southern California, Los Angeles, California 90089, United States

J. Phys. Chem. Lett., 2015, 6 (5), pp 913–917

DOI: 10.1021/acs.jpclett.5b00120

Publication Date (Web): February 24, 2015

Copyright © 2015 American Chemical Society

*E-mail: prezhdo@usc.edu (O.V.P.)., *E-mail: vvchaban@gmail.com (V.V.C.)., *E-mail: fileti@gmail.com (E.E.F.)

Energetic materials, such as explosives, propellants, and pyrotechnics, are widely used in civilian and military applications. Nanoscale explosives represent a special group because of the high density of energetic covalent bonds. The reactive molecular dynamics (ReaxFF) study of nitrofullerene decomposition reported here provides a detailed chemical mechanism of explosion of a nanoscale carbon material. Upon initial heating, C₆₀(NO₂)₁₂ disintegrates, increasing temperature and pressure by thousands of Kelvins and bars within tens of picoseconds. The explosion starts with NO₂ group isomerization into C–O–N–O, followed by emission of NO molecules and formation of CO groups on the buckyball surface. NO oxidizes into NO₂, and C₆₀ falls apart, liberating CO₂. At the highest temperatures, CO₂ gives rise to diatomic carbon. The study shows that the initiation temperature and released energy depend strongly on the chemical composition and density of the material.

 

http://pubs.acs.org/...jpclett.5b00120

 

[niner]

 

Buckybomb:

 

 

Yow!  I'm waiting for the first person to ask if they're going to blow up from taking too much c60oo.  Off topic but totally worth it.

[Kalliste]

Nightmare-scenario: C60 becomes known as an easy-to-use explosive chemical like fertilizer and is banned

[pone11]

I found a 2006 study on C60 fullerenes in vivo that predates Baati through an old post here on Longecity, and I added to that thread:

http://www.longecity...ition/?p=720036

 

I would urge anyone taking megadoses of C60 to read Table 1 in the Italian study I post at the bottom of that reply.  There are no dosing studies on C60, and the IAC study suggests that similar antioxidants can have a narrow range of benefit, with dramatic lifespan extension at the appropriate dose, and equally dramatic lifespan REDUCTION at slightly higher doses.

[pone11]

Does anyone have a list of studies that are trying to replication the Baati C60 result in rats?   Which of these are due to report back results this year?

[Razor444]

Does anyone have a list of studies that are trying to replication the Baati C60 result in rats?   Which of these are due to report back results this year?

 

There's the crowdfunded mouse study:

 

After many difficulties in setting the experiment (cross-border transportation in current geopolitical times, checking absorption in mice/ detecting C60/correct source of C60, administration tried in food and replaced by gavage, training for gavage and various measures) we have transposed the popular lifespan test with c60 fullerenes reported in rats by Baati et al. to mice (CBA strain, common in the lab) and with more animals (N=17 per group).

 

There are three groups (gavage of water, of olive oil, of C60 dissolved in olive oil), there are... a lot of health measures and a lot of gavage (at the beginnings of the experiment as administrations are first very frequent and then gradually less frequent). Given that the experiment starts with mid-aged animals, the results are expected for the beginning of 2016.

 

 

I read Fathi's group are attempting to replicate the initial results—but not sure if that's true.

 

I'm interested in the replication question myself. Or just more data per se!