Database Query Results : Silver-NanoParticles, Vitamin C (Ascorbic Acid),

SNP, Silver-NanoParticles: Click to Expand ⟱
Features:
Silver NanoParticles
Summary:
1. Smaller sizes desirable due to greater surface area, and cell penetration (enhanced permeability and retention (EPR) effect)
2. Two main types: AgNP and silver ions (big debate on uses: Ag+ turning to AgCl in stomach but AgCl also effective. Take sodium-bicarbonate?
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.”
4. AntiOxidants/NAC can counter act the effect of Silver NanoParticles from producing reactive oxygen species (ROS) and mitochondrial damage . NAC is a supplement form of cysteine, an amino acid that helps make glutathione, a powerful antioxidant.
5. In vitro most reports indicate AgNPs increase ROS in both cancer and normal cell (but in vivo improved antioxidant system of normal may create selectivity)
6. Pathways/mechanisms of action/:
-” intracellular ROS was increased...reduction in levels of glutathione (GSH)”
-”AgNPs affect the function of the vascular endothelial growth factor (VEGF)” (likely reducing levels)
-”expression of BAX and BCL2 genes was increased”
-”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.”

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.
Also may be true for Selenium(Sodium selenite) becuase of antioxidant properties, slowing oxidation of Ag0 to Ag+.
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               |



VitC, Vitamin C (Ascorbic Acid): Click to Expand ⟱
Features:
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)
Scientific Papers found: Click to Expand⟱
4539- SNP,  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
AntiCan↑, Significant cytotoxicity was observed in SKOV-3 ovarian cancer cells

4540- SNP,  VitC,    Silver nanoparticles from ascorbic acid: Biosynthesis, characterization, in vitro safety profile, antimicrobial activity and phytotoxicity
- in-vitro, Nor, NA
*Bacteria↓, AgNPs showed antibacterial activity against Gram-positive and Gram-negative strains.
*selectivity↑, AgNPs did not show cytotoxicity on VERO cells ranging from 0.5 to 150 μg mL−1 with a good gemoprotection.

4544- SNP,  VitC,    Current Research on Silver Nanoparticles: Synthesis, Characterization, and Applications
- Review, Nor, NA
*Bacteria↓, lity. The antimicrobial properties of Ag NPs are finding their application in enhancing the activity of drugs (like Amphotericin B, Nystatin, Fluconazole) and composite scaffolds for controlled release of drugs and targeted delivery of drugs due to t
*eff↑, 2]. However, mild reducing agents like ascorbic acid leads to the controlled growth of the Ag NP : ascorbic acid was added to reduce the remaining Ag + ions

4545- SNP,  VitC,  Citrate,    Ascorbic Acid-assisted Green Synthesis of Silver Nanoparticles: pH and Stability Study
- Study, NA, NA
*other↝, The synthesis of AgNPs was primarily identified by the appearance of yellow colour and confirmed by showing λmax =409 nm in UV-visible spectroscopy.
*other↝, In this study, the bottom-up strategy was used to synthesize AgNPs using ascorbic acid as a reductive agent and citric acid as a potent complex stabilizer, effectively.
*eff↑, It clearly explained that the reaction mixture having a pH at 10 is most appropriate to reduce Ag+ ions into AgNPs and stable over a month.
*eff↑, The FTIR results indicate that the citric acid is directly involved in the stabilization and capping of AgNPs, whereas ascorbic acid reduces Ag+ ions to Ag0.

4547- SNP,  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
*eff↑, the addition of Ag+ to AA-AuNPs solution (pH 10) resulted in naked-eye color transitions from red to orange and yellow, with a blue shift in the absorption maximum from 522 to 400 nm

4561- SNP,  VitC,    Cellular Effects Nanosilver on Cancer and Non-cancer Cells: Potential Environmental and Human Health Impacts
- in-vitro, CRC, HCT116 - in-vitro, Nor, HEK293
NRF2↑, Nanosilver increased Nrf2 protein expression and disrupted the cell cycle at the G1 and G2/M phases.
TumCCA↑, AgNPs interact with DNA to stop the cell cycle and lead to apoptosis
ROS↑, Nanosilver induced significant mitochondrial oxidative stress in HCT116, whereas it did not in the non-cancer HIEC-6 and nanosilver/sodium ascorbate co-treatment was preferentially lethal to HCT116 cells,
selectivity↑,
*AntiViral↑, AgNPs are effective antiviral agents against various viruses such as human immunodeficiency virus, hepatitis B virus, and monkey pox virus through interaction with surface glycoproteins on the virus
*toxicity↝, Citrate and PVP-coated AgNPs have been found to be less toxic than non-coated AgNPs
ETC↓, AgNPs affects mitochondrial function through the disruption of the electron transport chain2,24,26,33,39–41
MMP↓, Studies have shown that exposure to AgNPs resulted in a decrease of mitochondrial membrane potential (MMP) in various in vitro and in vivo experiments
DNAdam↑, AgNPs has also been shown to interact with and induce damage to DNA, DNA strand breaks, DNA damage
Apoptosis↑, apoptosis induced by AgNPs were through membrane lipid peroxidation, ROS, and oxidative stress
lipid-P↑,
other↝, Several studies have showed AgNPs interact with various proteins such as haemoglobin, serum albumin, metallothioneins, copper transporters, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), malate dehydrogenase (MDH), and bacterial proteins.
UPR↑, Studies have shown exposure to AgNPs induces activation of the UPR
*GRP78/BiP↑, AgNPs induced increased levels of GRP78, phosphorylated PERK, phosphorylated eIF2-α, and phosphorylated IRE1α, spliced XBP1, cleaved ATF-6, CHOP, JNK and caspase 12
*p‑PERK↑,
*cl‑eIF2α↑,
*CHOP↑,
*JNK↑,
Hif1a↓, One study showed AgNPs inhibits HIF-1 accumulation and suppresses expression of HIF-1 target genes in breast cancer cells (MCF-7) and also found the protein levels of HIF-1α and HIF-1β decreased
AntiCan↑, Many studies have shown that ascorbic acid, on its own, has anti-cancer effects
*toxicity↓, However, when the rats were treated with both ascorbic acid and AgNPs, a decrease in toxic effects was observed in non-cancer parotid glands in rats
eff↑, Studies have shown both AgNPs and ascorbic acid have greater effects and toxicity in cancer cells relative to non-cancer cells

4562- SNP,  VitC,    Eco-friendly Synthesis of Silver Nanoparticles using Ascorbic Acid and its Optical Characterization
- Study, NA, NA
*other↑, The Vitamin C (Ascorbic Acid) acts as a chemical reductant to successfully reduce silver ions into silver nanoparticles
*other↝, The optimized synthetic method utilizes higher pH conditions, sodium citrate as a silver ion stabilizer, hydrogen peroxide as an etching agent, and ascorbic acid as a reducing agent, allowing nanoscale-sized silver particles to be achieved even at t


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Results for Effect on Cancer/Diseased Cells:
AntiCan↑,2,   Apoptosis↑,1,   DNAdam↑,1,   eff↑,1,   ETC↓,1,   Hif1a↓,1,   lipid-P↑,1,   MMP↓,1,   NRF2↑,1,   other↝,1,   ROS↑,1,   selectivity↑,1,   TumCCA↑,1,   UPR↑,1,  
Total Targets: 14

Results for Effect on Normal Cells:
AntiViral↑,1,   Bacteria↓,2,   CHOP↑,1,   eff↑,4,   cl‑eIF2α↑,1,   GRP78/BiP↑,1,   JNK↑,1,   other↑,1,   other↝,3,   p‑PERK↑,1,   selectivity↑,1,   toxicity↓,1,   toxicity↝,1,  
Total Targets: 13

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