Welcome, we OEM manufacturer wholesale price

Silver Quantum Dots Enhance Liver Absorption and Therapeutic Effectiveness of NMN and Metformin

Author: GSHWORLD Release time: 2021-03-08 Column: Product News



   Attaching NMN and metformin to silver nanocrystals called quantum dots significantly enhances their uptake into liver cells.

   The quantum dot-bound NMN and metformin facilitate improved metabolic responses like blood glucose clearance at much lower drug doses.


(Hunt et al., 2021 | ACS NanoOral quantum dot-attached NMN and metformin substantially increases liver cell uptake of the therapeutic agents and enhances their potency. NMN and metformin were loaded onto silver nanocrystal quantum dots and administered orally through water. Their enhanced liver cell uptake and potency drive improved sugar glucose clearance from the blood.


Nanomedicine is the application of nanotechnology – technology dealing with tiny dimensions of less than 100 nanometers – to therapeutic agents. Some believe biotechnology research has reached “the beginning of the end of the nanomedicine hype” mostly due to the lack of nanotechnology’s translation to treat cancer. At the same time, since 80-95% of nanomaterials accumulate in and are cleared by the liver, others propose nanomedicines have considerable promise in targeting liver diseases and metabolic disorders. Whether nanotechnology application to therapeutics targeting liver disease and metabolic disorders enhances their effectiveness remains to be explored.

Cogger and colleagues from the University of Sydney in Australia published a study in ACS Nano demonstrating that attaching Nicotinamide Mononucleotide (NMN) and metformin to silver nanocrystals called quantum dots substantially enhances their uptake in the liver. The quantum dot-bound medicines also facilitate an improved metabolic response to the sugar glucose, indicative of enhanced metabolism. Enhanced drug delivery and potency with quantum dots may translate to improved drug delivery methods for aged individuals with metabolic or liver disease.

The Effects from NMN and Metformin Treatment

NMN is a precursor to the vital molecule nicotinamide adenine dinucleotide (NAD+) that has essential roles in cell energy-generating processes. By increasing NAD+ levels in mice, NMN can also drive the activation of proteins dependent on NAD+ called sirtuins that promote metabolism.

The other quantum dot-conjugated drug explored in the study, metformin, is extensively prescribed for type 2 diabetes. It increases lifespan in animal models by adding a molecular tag and thereby activating the enzyme referred to as adenosine monophosphate-activated protein kinase (AMPK). AMPK triggers the uptake of glucose when cellular energy is low thereby enhancing metabolism.

NMN’s stimulation of sirtuin function and metformin’s activation of AMPK can both promote improved metabolic function. To find out if binding NMN and metformin to quantum dots for oral drug delivery through water consumption improves their potency, Cogger and colleagues measured the cellular uptake of the quantum dot-bound pharmaceuticals along with the clearance of the sugar glucose in blood.

Quantum DotsEnhance Liver Cell Absorption of Metformin

The Australia-based research group first examined quantum dot-bound metformin uptake in the liver. They saw expedited absorption with higher cell metformin concentrations in liver cells following oral ingestion. While metformin alone peaked at eight hours after consumption, the quantum dot metformin levels peaked much more quickly at about two hours. Quantum dot binding to metformin also enhanced the total amount of metformin that the liver absorbed. These findings indicate that quantum dots substantially improve therapeutic agent absorption in the liver with faster uptake in greater quantities.

(Hunt et al., 2021 | ACS NanoMetformin loaded onto quantum dots has faster liver cell uptake in greater quantities. The left graph shows liver cell metformin quantum dot absorption over a 24-hour time course. The metformin quantum dots increased in abundance with peak levels at approximately two hours (red line). Metformin on its own showed peak levels at about eight hours (black line). The grey line represents quantum dot uptake without metformin attached. The right graph shows total metformin quantum dot liver cell absorption (red bar) compared to quantum dots on their own (grey bar) and metformin on its own (black bar). Attaching metformin to quantum dots sped up its absorption with higher absorption levels.


Less NMN and Metformin Are Needed with Quantum Dots to Clear Blood Glucose

Cogger and colleagues then found that the medicines conjugated to quantum dots provided significantly reduced blood glucose levels in tolerance tests for the sugar that measure the body’s ability to clear it. Glucose tolerance tests measure blood sugar concentrations after ingesting a glucose solution, and type 2 diabetes patients cannot typically clear blood glucose. To achieve the same glucose tolerance test results in mice, the metformin dose required with quantum dots was 100 times less than that of metformin alone. NMN, although not as potent at inducing glucose clearance, required a thousand times less of a dose compared to NMN alone. These findings indicate that quantum dots greatly enhance therapeutic agent absorption so that drastically diminished doses of the medicine are required with quantum dots.

(Hunt et al., 2021 | ACS NanoNMN and metformin attached to quantum dots enhanced the potency of the drugs. The optimal dose of metformin for glucose clearance was 100 mg/kg (solid black line, A) while the optimal dose for quantum dot metformin was 2.4 mg/kg (solid red line, B). Dose curves indicated that 100-fold less quantum dot metformin was required to clear glucose from the blood (C). Metformin quantum dots cleared blood glucose in greater quantities than metformin on its own when administered at the same dose (D). NMN on its own cleared blood glucose optimally at a dose of 6000 mg/kg (solid dark green line, E). Quantum dot-attached NMN cleared glucose blood levels optimally at 7.8 mg/kg (dark blue line, F). The dose curves indicate that quantum dot conjugated NMN required 1000-fold less NMN than NMN alone to clear blood glucose (G). When administered at the same dose, quantum dot bound NMN significantly reduced glucose in the blood more than NMN on its own (H).


Clathrin Proteins Mediate Cellular Quantum Dot Uptake

To see out how quantum dots improve uptake, Cogger and colleagues examined how cells absorbed these compounds. They found liver cells use a cellular uptake mechanism utilizing proteins that create small sacs to absorb the quantum dots called clathrin-mediated endocytosis.  The medicines can bypass cellular transporters that typically absorb them and instead get absorbed by clathrin-mediated endocytosis. For example, the transporter OCT1 absorbs metformin on its own, but inhibiting OCT1 did not reduce the uptake of quantum dot-bound metformin. This shows that quantum dot conjugated medicines could have better uptake by getting around their typical absorption transporters, which can deteriorate with age. Bypassing deteriorating transporters for medicine absorption with quantum dot-bound medicines could provide a means to enhance medicine uptake in aged individuals.

“We show that [quantum dot]-metformin and [quantum dot]-NMN have dramatically increased hepatic bioavailability and 100- to 1000-fold improvements in metabolic effects compared to drug alone,” stated Cogger and colleagues in their publication.

Future Nanomedicine Research on Liver Dysfunction

Based on their findings, the research team says quantum dots are ideal for nanotherapeutic development. More work should be geared toward developing nanotherapeutics that target the liver, rather than other organs, since the liver absorbs and clears most nanomedical agents.

*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.


Tag: NMN , Therapeutic Effectiveness

GSH BIO-TECH API Pharmaceutical Intermediates Cosmetic Raw Materials, GSH World