Iron nanoparticles can activate the immune system to attack cancer cells, according to a study led by researchers at the Stanford University School of Medicine.

The mouse study found that ferumoxytol prompts immune cells called tumor-associated macrophages to destroy cancer cells, suggesting that the nanoparticles could complement existing cancer treatments. The discovery, described in a paper published online Sept. 26 in Nature Nanotechnology, was made by accident while testing whether the nanoparticles could serve as Trojan horses by sneaking chemotherapy into tumors in mice. [link to www.sciencedaily.com (secure)]


{ cancer cell } <-- [macrophage] <-- | nano-Fe |

So, what of Tg, (), in [macrophage] ?

{ cancer cell } <-- [ma()crop()h()age] <-- | nano-Fe |

Maybe we should be wondering:

- Does the added nano-Fe participate in catalysis and accelerate Tg growth? Or poison and decatalyze?
- How does Tg react?
- What happens to Tg during and after cancer cell consumption?



Eq. (1a): O2- + H+ + SOD.M3+.OH- -------> O2 + SOD.M2+.OH2

Eq. (1b): O2- + H+ + SOD.M2+.OH2 -------> H2O2 + SOD.M3+.OH-

The higher Em of high-spin Mn3+/Mn2+ explains its lower Fenton reactivity than Fe and makes it a safer metal ion for use under conditions of oxidative stress. However a high Em also makes it inefficient in SOD activity. The ideal m for a SOD would be half-way between the ms of SOD's two half-reactions, near 360 mV vs. the normal hydrogen electrode (NHE). A metal site with too low an Em will be able to reduce superoxide (Eq. (1b)) but will not be able to extract an electron from superoxide (Eq. (1a)). A site with too high an Em will be able to oxidize superoxide (Eq. (1a)), but will not be able to pass the gained electron on to a second molecule of superoxide (Eq. (1b)). Both types of site can consume superoxide but only stoichiometrically, unless they are regenerated by other electron transport systems. Yet part of the elegance and biochemical economy of SODs is their independence from any electron donor or acceptor. This allows them to function as stand-alone antioxidant defenses and also to consume two equivalents of superoxide per turnover.
...
The proton taken up in conjunction with metal ion reduction is understood to be acquired by the coordinated solvent [25] so that the redox reaction is correctly written M3+•OH- + e- + H+ == M2+•OH2. Because coordinated OH- is a better ligand for Fe3+ (and Mn3+) than for Fe2+ (and Mn2+), I proposed that the active site of (Mn)SOD might suppress metal ion reduction (and the Em) by disfavouring protonation of coordinated solvent [20, 22, 34]. [link to febs.onlinelibrary.wiley.com (secure)]


As such iron reduction:

Eq. (1a'): (O2)- + H+ + SOD.Fe3+.OH- -------> O2 + SOD.Fe2+.OH2

Oxidation:

Eq. (1b'): (O2)- + H+ + SOD.Fe2+.OH2 -------> H2O2 + SOD.Fe3+.OH-

hydroxl and peroxide - jet fuel (or in necrosis, alcohol and debriding/sloughing agent)

However the host proteins must control this broad reactivity, activating the metal for the intended reaction while excluding the rest of its chemical repertoire. To this end, metalloproteins must control the metal ion reduction midpoint potential (Em), because the Em determines what redox reactions are possible. [link to pubs.acs.org (secure)]

Fe3+·OH- and Fe2+·OH2

Note: Between suppression of reduction when Mn is substituted in the metalloenzyme and ionic Mn-S bonding, manganese is a douple edged sword.

Sodium nitroprusside - well-known inducer of bradyzoite differentiation; reduced reporter parasite replication and caused bradyzoite differentiation. Stress-induced differentiation in many other pathogens is regulated by cyclic nucleotide kinases. [link to www.researchgate.net (secure)]

In vitro stresses induce stage conversion
It is well documented that conversion to the latent stage is a stress-mediated response, coupled with a slowing of the parasite cell cycle. One of the most commonly used in vitro methods to prompt bradyzoite differentiation is alkaline pH 8.0–8.2 (Soete, et al., 1994). A wide variety of other stress agents have since been reported, including sodium nitroprusside, which acts as a source of exogenous nitric oxide (NO) and also inhibits proteins involved in the parasite mitochondrial respiratory chain (Bohne, et al., 1994). Similarly, drugs that interfere with the parasite mitochondria also induce differentiation to bradyzoites (Bohne, et al., 1994, Tomavo & Boothroyd, 1995). Heat shock and treatment with sodium arsenite also trigger expression of bradyzoite antigens (Soete, et al., 1994). Nutrient deprivation is a potent inducer of bradyzoite formation and can be achieved through arginine starvation (Fox, et al., 2004), axenic incubation (Yahiaoui, et al., 1999), or pyrimidine depletion in uracil phosphoribosyltransferase (UPRT)-deficient parasites subjected to ambient (0.03%) CO2 (Bohne & Roos, 1997, Dzierszinski, et al., 2004). More recently, insults that cause endoplasmic reticulum (ER) stress or that interfere with calcium-induced egress have also been found to induce bradyzoite cyst formation (Nagamune, et al., 2008, Narasimhan, et al., 2008). Treatment with IFN-? does not induce conversion to bradyzoites cultured in human fibroblasts (Soete, et al., 1994), but will do so in murine macrophages, presumably due to the stimulated releases of NO (Bohne, et al., 1993). Long-term culturing of cysts was accomplished in vitro using murine astrocytes and intermittent inclusion of IFN-? in the culture media (Jones, et al., 1986). [link to www.ncbi.nlm.nih.gov (secure)]


Calcium plays crucial roles in important events of Toxoplasma gondii life cycle, including motility, invasion and egress from the host cell. Calcium ionophore has been used to artificially trigger release of the parasites from infected cells. [link to www.sciencedirect.com (secure)]

Calcium ionophore, A23187, mobile ion-carrier forms stable complexes with divalent cations, allowing ions to cross membranes.

So can also assist in shuttling reduction products:
Eq. (1a'): (O2)- + H+ + SOD.Fe3+.OH- -------> O2 + SOD.Fe2+.OH2

(SOD.Fe2+.OH2) + A23187 + 2e- == SOD.OH2.FE.A23187

But specific to Ca: Ca2+ + A23187 + 2e- == Ca.A23187 ready for egress

Ca(2+)-mediated signaling events modulate key steps required for host cell egress, invasion and motility, including secretion of microneme organelles and activation of the force-generating actomyosin-based motor. [link to www.researchgate.net (secure)]

Calcium ions thus being required for activity, Ca-depletion becomes of interest.


[link to www.godlikeproductions.com]

Another triterpene.

Also from Feb. 2019: Isolation, structure determination and structure–activity relationship of anti-toxoplasma triterpenoids from Quercus crispula Blume outer bark; [link to link.springer.com (secure)]