tbResList Print — AgNPs Silver-NanoParticles

Description: <b>Silver NanoParticles (AgNPs)</b><br>
Summary: <br>
1.Smaller sizes are generally more bioactive due to increased surface area and enhanced tumor accumulation via the enhanced permeability and retention (EPR) effect.<br>
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.<br>
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)<br>
Likely 10ppm --> 10mg/L, hence if take 100mL, then 1mg/day? (for Cancer)<br>
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.<br>
Seems like the Cancer target range is 14ug/kg/day to 25ug/kg/day. 80Kg example: 1.12mg to 2mg
<a href="https://www.cancertreatmentsresearch.com/a-silver-bullet-to-kill-cancer/" > “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.” </a> <br>
These values reflect experimental or anecdotal contexts and are not established safe or therapeutic doses.<br>
4. Antioxidants such as NAC can counteract AgNP cytotoxicity by restoring glutathione pools and suppressing ROS-mediated mitochondrial damage. <br>
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.<br>
6. Pathways/mechanisms of action/:<br>
-” intracellular ROS was increased...reduction in levels of glutathione (GSH)”<br>
- Normal-cell selectivity is partly mediated by NRF2-dependent antioxidant and detoxification responses.<br>
- AgNPs impair mitochondrial electron transport, increasing electron leak and amplifying ROS upstream of ΔΨm collapse.<br>
-AgNPs inhibit VEGF-driven endothelial signaling and permeability (anti-angiogenic effect)<br>
-”upregulation of proapoptotic genes (p53, p21, Bax, and caspases) and downregulation of antiapoptotic genes (Bcl-2)”<br>
-” upregulation of AMPK and downregulation of mTOR, MMP-9, BCL-2, and α-SMA”<br>
-”p53 is a key player...proapoptotic genes p53 and Bax were significantly increased... noticeable reduction in Bcl-2 transcript levels”<br>
-” p53 participates directly in the intrinsic apoptosis pathway by regulating the mitochondrial outer membrane permeabilization”<br>
- “Proapoptotic markers (BAX/BCL-XL, cleaved poly(ADP-ribose) polymerase, p53, p21, and caspases 3, 8 and 9) increased.”<br>
-”The antiapoptotic markers, AKT and NF-kB, decreased in AgNP-treated cells.”<br>
<br>
Chronic accumulation and long-term systemic effects remain insufficiently characterized.<br>
<br>
Silver NanoParticles and Magnetic Fields<br>
Summary:<br>
1. “exposure to PMF increased the ability of AgNPs uptake”<br>
2. 6x improvement from AgNPs alone<br>
<br>
could
<a href="https://nestronics.ca/dbx/tbResList.php?qv=335&qv2=153&wNotes=on&">glucose </a>
capping of SilverNPs work as trojan horse?<br>
<br>
<a href="https://nestronics.ca/dbx/tbResEdit.php?rid=4434">Sodium selenite might protect against toxicity
of AgNPs in normal cells.</a> <br>
<br>
-uncoated AgNPs can degrade the gut microbiome. PVP, citrate, green-synthesized, chitosan coating, may reduce
the effect. <br>
Similar oxidative considerations may apply to selenium compounds, though mechanisms differ.<br>
co-ingestion with food (higher pH) favors reduction and lower Ag+ levels. <br>

-action mechanisms of AgNPs: the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure. <br>
<br>
AgNP anticancer effects come from three overlapping mechanisms:<br>
-Nanoparticle–cell interaction (uptake, membrane effects)<br>
-Intracellular ROS generation<br>
-Controlled Ag⁺ release inside cancer cells<br>
<br>
<pre>
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 |
</pre>
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<table >
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>

<tr>
<td>1</td>
<td>Oxidative stress / ROS generation</td>
<td>↑ ROS (sustained)</td>
<td>↑ transient ROS → ↓ net ROS after adaptation</td>
<td>Upstream cytotoxic trigger</td>
<td>AgNP exposure commonly elevates ROS in cancer cells, initiating downstream stress-death programs</td>
<td><a href="https://pubs.acs.org/doi/10.1021/acsomega.7b00045" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>2</td>
<td>Thiol buffering (GSH pool)</td>
<td>↓ GSH (depletion)</td>
<td>↔ or transient ↓ with recovery</td>
<td>Loss of redox buffering</td>
<td>Colon cancer model: AgNPs induce oxidative cell damage through inhibition/depletion of reduced glutathione with downstream mitochondrial apoptosis</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/30056045/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>3</td>
<td>Mitochondrial ETC / respiration</td>
<td>↓ ETC efficiency; ↑ electron leak</td>
<td>↔ mild inhibition with recovery</td>
<td>Bioenergetic destabilization</td>
<td>ETC impairment amplifies ROS, precedes ΔΨm loss, and contributes to ATP collapse in cancer cells</td>
<td></td>
</tr>

<tr>
<td>4</td>
<td>Mitochondrial integrity (ΔΨm / MMP)</td>
<td>↓ ΔΨm</td>
<td>↔ largely preserved</td>
<td>Mitochondrial dysfunction</td>
<td>Breast cancer model: AgNP exposure dissipates mitochondrial membrane potential during cytotoxic progression</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6156419/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>5</td>
<td>Intrinsic apoptosis (caspase cascade)</td>
<td>↑ caspase-dependent apoptosis</td>
<td>↔ minimal activation</td>
<td>Programmed cell death</td>
<td>Colon cancer model: “silver-based nanoparticles” induce apoptosis mediated through p53 (apoptosis direction shown)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/23514434/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>6</td>
<td>Genotoxic stress / DNA damage</td>
<td>↑ DNA damage</td>
<td>↑ damage at high dose with efficient repair</td>
<td>Checkpoint/death signaling</td>
<td>Study documents AgNP-mediated DNA damage; susceptibility increases with impaired DNA repair capacity</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5890915/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>7</td>
<td>ER stress / UPR (CHOP-dependent)</td>
<td>↑ ER stress → apoptosis</td>
<td>↑ adaptive UPR (no CHOP)</td>
<td>Proteotoxic stress signaling</td>
<td>Breast cancer cells: AgNPs induce “irremediable” ER stress leading to UPR-dependent apoptosis</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/27586505/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>8</td>
<td>Autophagy program</td>
<td>↑ autophagy (protective)</td>
<td>↑ adaptive autophagy</td>
<td>Stress adaptation</td>
<td>AgNPs induce autophagy in cancer cells; inhibiting autophagy enhances AgNP anticancer killing</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4502813/" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>9</td>
<td>Autophagic flux / lysosomal function</td>
<td>↓ flux (lysosomal defect)</td>
<td>↔ preserved flux</td>
<td>Autophagic failure</td>
<td>AgNP-induced lysosomal dysfunction drives autophagic flux defects (LC3-II accumulation)</td>
<td><a href="https://academic.oup.com/toxsci/article/150/2/473/2461967" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>10</td>
<td>NRF2 antioxidant response</td>
<td>↔ insufficient activation</td>
<td>↑ NRF2 activation</td>
<td>Adaptive redox defense</td>
<td>NRF2 activation in normal cells restores GSH and antioxidant enzymes, limiting toxicity</td>
<td></td>
</tr>

<tr>
<td>11</td>
<td>Stress MAPK (p38) / checkpoint signaling</td>
<td>↑ p38 → arrest/apoptosis</td>
<td>↑ transient p38 → recovery</td>
<td>Stress signaling</td>
<td>Jurkat T-cell model shows p38 MAPK activation with DNA damage and apoptosis</td>
<td><a href="https://pubs.acs.org/doi/abs/10.1021/es1020668" target="_blank">(ref)</a></td>
</tr>

<tr>
<td>12</td>
<td>Angiogenesis / invasion (VEGF, NF-κB-linked)</td>
<td>↓ angiogenesis / ↓ invasion</td>
<td>↔ minimal effect</td>
<td>Anti-angiogenic / anti-invasive</td>
<td>AgNPs inhibit VEGF-induced permeability and invasion in tumor models</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2776000/" target="_blank">(ref)</a></td>
</tr>

</table>