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| Silver NanoParticles (AgNPs) Summary: 1.Smaller sizes are generally more bioactive due to increased surface area and enhanced tumor accumulation via the enhanced permeability and retention (EPR) effect. 2.Two relevant forms: particulate silver (AgNPs) and ionic silver (Ag⁺). There is debate regarding oral use, as Ag⁺ can precipitate as AgCl in gastric acid, reducing bioavailability; AgNPs may partially avoid this via particulate uptake and intracellular Ag⁺ release. Gastric pH may influence this equilibrium. 3. Dose example 80kg person: 1.12-2mg/day, which can be calculated based on ppm and volume taken (see below) target < 10ppm and 120mL per day (30ppm and 1L per day caused argyria 30mg/day ) (Case Report: 9‐15 ppm@120mL, i.e. 1.1mg/L to 1.8mg/L per day) Likely 10ppm --> 10mg/L, hence if take 100mL, then 1mg/day? (for Cancer) The current Rfd for oral silver exposure is 5 ug/kg/d with a critical dose estimated at 14 ug/kg/d for the average person. Seems like the Cancer target range is 14ug/kg/day to 25ug/kg/day. 80Kg example: 1.12mg to 2mg “1.4µg/kg body weight. If I would have 70kg, I would want to use 100µg/day. However, for fighting active disease, I would tend to explore higher daily dose, as I think this may be too low.” These values reflect experimental or anecdotal contexts and are not established safe or therapeutic doses. 4. Antioxidants such as NAC can counteract AgNP cytotoxicity by restoring glutathione pools and suppressing ROS-mediated mitochondrial damage. 5. In vitro studies commonly show ROS elevation in both cancer and normal cells; however, in vivo, superior antioxidant, NRF2, and repair capacity in normal tissues may confer selectivity. 6. Pathways/mechanisms of action/: -” intracellular ROS was increased...reduction in levels of glutathione (GSH)” - Normal-cell selectivity is partly mediated by NRF2-dependent antioxidant and detoxification responses. - AgNPs impair mitochondrial electron transport, increasing electron leak and amplifying ROS upstream of ΔΨm collapse. -AgNPs inhibit VEGF-driven endothelial signaling and permeability (anti-angiogenic effect) -”upregulation of proapoptotic genes (p53, p21, Bax, and caspases) and downregulation of antiapoptotic genes (Bcl-2)” -” upregulation of AMPK and downregulation of mTOR, MMP-9, BCL-2, and α-SMA” -”p53 is a key player...proapoptotic genes p53 and Bax were significantly increased... noticeable reduction in Bcl-2 transcript levels” -” p53 participates directly in the intrinsic apoptosis pathway by regulating the mitochondrial outer membrane permeabilization” - “Proapoptotic markers (BAX/BCL-XL, cleaved poly(ADP-ribose) polymerase, p53, p21, and caspases 3, 8 and 9) increased.” -”The antiapoptotic markers, AKT and NF-kB, decreased in AgNP-treated cells.” Chronic accumulation and long-term systemic effects remain insufficiently characterized. Silver NanoParticles and Magnetic Fields Summary: 1. “exposure to PMF increased the ability of AgNPs uptake” 2. 6x improvement from AgNPs alone could glucose capping of SilverNPs work as trojan horse? Sodium selenite might protect against toxicity of AgNPs in normal cells. -uncoated AgNPs can degrade the gut microbiome. PVP, citrate, green-synthesized, chitosan coating, may reduce the effect. Similar oxidative considerations may apply to selenium compounds, though mechanisms differ. co-ingestion with food (higher pH) favors reduction and lower Ag+ levels. -action mechanisms of AgNPs: the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure. AgNP anticancer effects come from three overlapping mechanisms: -Nanoparticle–cell interaction (uptake, membrane effects) -Intracellular ROS generation -Controlled Ag⁺ release inside cancer cells Comparison adding Citrate Capping | Property | Uncapped AgNPs | Citrate-capped AgNPs | | --------------------- | -------------- | -------------------- | | Stability | Poor | Excellent | | Free Ag⁺ | High | Low | | Normal cell toxicity | Higher | Lower | | Cancer selectivity | Lower | **Higher** | | Mechanism specificity | Crude | **Targeted** | | Storage behavior | Degrades | Stable |
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| High-dose vitamin C: Some studies have suggested that high-dose vitamin C may be effective in treating certain types of cancer, such as ovarian cancer and pancreatic cancer. Symptoms of vitamin C deficiency include fatigue, weakness, poor wound healing, ecchymoses, xerosis, lower extremity edema, and musculoskeletal pain—most of them are often observed in end-stage cancer patients. -Vitamin C is an essential nutrient involved in the repair of tissue, the formation of collagen, and the enzymatic production of certain neurotransmitters. It is required for the functioning of several enzymes and is important for immune system function. -Ascorbic Acid, Different levels in different Organs Homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. -(Note the Oncomagnetic success in the brain also was then under conditions of high Vitamin C) -Ascorbic acid is an electron donor Ascorbic Acid, can be a Pro-oxidant "The pro-oxidative activity of ascorbic acid (Figure 2) is associated with the interaction with transition metal ions (especially iron and copper). Under conditions of high, millimolar ascorbate concentration, vitamin C catalyzes the reduction of free transition metal ions, which causes the formation of oxygen radicals." Ascorbic Acid, formation of H2O2 (Hydrogen Peroxide) Many studies indicate the toxicity of ascorbate to cancer cells. Much evidence indicates that the underlying phenomenon is the pro-oxidative activity of ascorbate, which induces the formation of H2O2 and oxidative stress. "ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2)" -High dose VitC therapy may not be for those with kidney problems -Oral supplement up to 10g/day? -Direct regulator of TET↑ -caution for (G6PD-) deficient patients receiving vitamin C infusions -Note plasma half-life 30mins to 1hr, 1.5-2hr elimination half-life. oral BioAv water soluble, but has limitiations as 100mg yeilds 60uM/L in plasma, but 1000mg only yeilds 85uM/L. mM concentration are required for effectiveness on cancer cells. Hence why IV administration is common. Boosting HIF increases the intracellular uptake of oxidized VitC Pathways: - high dose induces ROS production in cancer cells. Otherwise well known antioxidant in normal cells. - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Caspases↑, DNA damage↑, cl-PARP↑, - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓ - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, NF-κB↓, - reactivate genes thereby inhibiting cancer cell growth : P53↑, TET↑ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TET1↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, GRP78↑, Glucose↓, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, - Others: PI3K↓, AKT↓, STAT↓, AMPK, ERK↓, JNK, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Hepatoprotective, - Selectivity: Cancer Cells vs Normal Cells Selenium supplementation may protect cells against iron-dependent cell death by supporting increased expression of selenoproteins, including GPX4, which defend against oxidative stress. Meaning it may decrease effectiveness of high dose VitC.(#4468) |
| 4539- | AgNPs, | VitC, | Citrate, | Investigating the Anti-cancer Potential of Silver Nanoparticles Synthesized by Chemical Reduction of AgNO3 Using Trisodium Citrate and Ascorbic Acid |
| - | in-vitro, | Nor, | L929 | - | in-vitro, | Ovarian, | SKOV3 |
| 4540- | AgNPs, | VitC, | Silver nanoparticles from ascorbic acid: Biosynthesis, characterization, in vitro safety profile, antimicrobial activity and phytotoxicity |
| - | in-vitro, | Nor, | NA |
| 4544- | AgNPs, | VitC, | Current Research on Silver Nanoparticles: Synthesis, Characterization, and Applications |
| - | Review, | Nor, | NA |
| 4545- | AgNPs, | VitC, | Citrate, | Ascorbic Acid-assisted Green Synthesis of Silver Nanoparticles: pH and Stability Study |
| - | Study, | NA, | NA |
| 4547- | AgNPs, | GoldNP, | VitC, | Exploration of Biocompatible Ascorbic Acid Reduced and Stabilized Gold Nanoparticles, as Sensitive and Selective Detection Nanoplatform for Silver Ion in Solution |
| - | Study, | NA, | NA |
| 4561- | AgNPs, | VitC, | Cellular Effects Nanosilver on Cancer and Non-cancer Cells: Potential Environmental and Human Health Impacts |
| - | in-vitro, | CRC, | HCT116 | - | in-vitro, | Nor, | HEK293 |
| 4562- | AgNPs, | VitC, | Eco-friendly Synthesis of Silver Nanoparticles using Ascorbic Acid and its Optical Characterization |
| - | Study, | NA, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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