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Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model
Hector Katifelis1, Iuliia Mukha2, Penelope Bouziotis3
1Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Purpose:
To evaluate the antitumor efficacy of Ag3Au1Trp1:2NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor's metastatic potential and the underlying molecular mechanism.
Subjects And Methods:
Ag3Au1Trp1:2NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag3Au1Trp1:2NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively.
Results:
In the 4T1 tumor-bearing SCID mice, Ag3Au1Trp1:2NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels.
Conclusion:
Based on our results, Ag3Au1Trp1:2NPs express anti-tumor and anti-metastatic effects in vivo. Ag3Au1Trp1:2NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway.
Insights
Silver-gold-tryptophan nanoparticles (Ag3Au1Trp1:2NPs) demonstrated significant antitumor and antimetastatic effects in a mouse cancer model. These nanoparticles selectively induce cancer cell apoptosis via the TRAIL-dependent pathway.
Area of Science:
- Nanomedicine
- Cancer Research
- Molecular Biology
Background:
- Nanoparticles (NPs) offer novel therapeutic strategies for cancer treatment.
- Targeted delivery of therapeutic agents to tumors is crucial for efficacy and minimizing side effects.
Purpose of the Study:
- To evaluate the antitumor and antimetastatic efficacy of silver-gold-tryptophan nanoparticles (Ag3Au1Trp1:2NPs) in a SCID mouse cancer model.
- To investigate the molecular mechanisms underlying the observed therapeutic effects.
Main Methods:
- Ag3Au1Trp1:2NPs were radiolabeled with Gallium-68 for biodistribution studies.
- Tumor growth was monitored, and metastatic potential was assessed in lung and liver tissues.
- Caspase-3 and TRAIL expression levels were analyzed using real-time PCR and Western blot.
Main Results:
- Ag3Au1Trp1:2NPs exhibited rapid accumulation at tumor sites.
- The highest dose of Ag3Au1Trp1:2NPs reduced tumor volume by 1.9-fold compared to controls.
- NPs treatment inhibited metastasis to the liver and lungs and increased Caspase-3 and TRAIL levels.
Conclusions:
- Ag3Au1Trp1:2NPs possess significant in vivo antitumor and antimetastatic properties.
- The nanoparticles induce cancer cell apoptosis through the extrinsic TRAIL-dependent pathway.
- Enhanced tumor targeting and retention contribute to the observed therapeutic effects.
