Silver Nanoparticles Inhibit Metastasis of 4T1 Tumor in Mice after Intragastric but Not Intravenous Administration.

The potential anticancer activity of different silver nanoformulations is increasingly recognized. In the present work, we use the model of 4T1 tumor in BALB/ccmdb immunocompetent mice to analyze the impact of citrate- and PEG-coated silver nanoparticles (AgNPs) on the development and metastatic potential of breast cancer. One group of mice was intragastrically administered with 1 mg/kg body weight (b.w.) of AgNPs daily from day 1 to day 14 after cancer cells implantation (total dose 14 mg/kg b.w.). The second group was intravenously administered twice with 1 or 5 mg/kg b.w. of AgNPs. A tendency for lowering tumor volume on day 21 (mean volumes 491.31, 428.88, and 386.83 mm3 for control, AgNPs-PEG, and AgNPs-citrate, respectively) and day 26 (mean volumes 903.20, 764.27, and 672.62 mm3 for control, AgNPs-PEG, and AgNPs-citrate, respectively) has been observed in mice treated intragastrically, but the effect did not reach the level of statistical significance. Interestingly, in mice treated intragastrically with citrate-coated AgNPs, the number of lung metastases was significantly lower, as compared to control mice (the mean number of metastases 18.89, 14.90, and 8.03 for control, AgNPs-PEG, and AgNPs-citrate, respectively). No effect of AgNPs treatment on the number of lung metastases was observed after intravenous administration (the mean number of metastases 12.44, 9.86, 12.88, 11.05, and 10.5 for control, AgNPs-PEG 1 mg/kg, AgNPs-PEG 5 mg/kg, AgNPs-citrate 1 mg/kg, and AgNPs-citrate 5 mg/kg, respectively). Surprisingly, inhibition of metastasis was not accompanied by changes in the expression of genes associated with epithelial-mesenchymal transition. Instead, changes in the expression of inflammation-related genes were observed. The presented results support the antitumor activity of AgNPs in vivo, but the effect was limited to the inhibition of metastasis. Moreover, our results clearly point to the importance of AgNPs coating and route of administration for its anticancer activity. Finally, our study supports the previous findings that antitumor AgNPs activity may depend on the activation of the immune system and not on the direct action of AgNPs on cancer cells.

Transient Vasodilation in Mouse 4T1 Tumors after Intragastric and Intravenous Administration of Gold Nanoparticles.

Gold nanoparticles (AuNPs) are foreseen as a promising tool in nanomedicine, both as drug carriers and radiosensitizers. They have been also proposed as a potential anticancer drug due to the anti-angiogenic effect in tumor tissue. In this work we investigated the effect of citrate-coated AuNPs of nominal diameter 20 nm on the growth and metastatic potential of 4T1 cells originated from a mouse mammary gland tumor inoculated into the mammary fat pad of Balb/ccmdb mice. To evaluate whether AuNPs can prevent the tumor growth, one group of inoculated mice was intragastrically (i.g.) administered with 1 mg/kg of AuNPs daily from day 1 to day 14 after cancer cell implantation. To evaluate whether AuNPs can attenuate the tumor growth, the second group was intravenously (i.v.) administered with 1 or 5 mg/kg of AuNPs, twice on day 5 and day 14 after inoculation. We did not observe any anticancer activity of i.v. nor i.g. administered AuNPs, as they did not affect neither the primary tumor growth rate nor the number of lung metastases. Unexpectedly, both AuNP treatment regimens caused a marked vasodilating effect in the tumor tissue. As no change of potential angiogenic genes (Fgf2, Vegfa) nor inducible nitric oxygenase (Nos2) was observed, we proposed that the vasodilation was caused by AuNP-dependent decomposition of nitrosothiols and direct release of nitric oxide in the tumor tissue.

Detection of E. coli labeled with metal-conjugated antibodies using lateral-flow assay and laser-induced breakdown spectroscopy.

This study explores the adoption of laser-induced breakdown spectroscopy (LIBS) for the analysis of lateral-flow immunoassays (LFIAs). Gold (Au) nanoparticles are standard biomolecular labels among LFIAs, typically detected via colorimetric means. A wide diversity of lanthanide-complexed polymers (LCPs) are also used as immunoassay labels but are inapt for LFIAs due to lab-bound detection instrumentation. This is the first study to show the capability of LIBS to transition LCPs into the realm of LFIAs, and one of the few to apply LIBS to biomolecular label detection in complete immunoassays. Initially, an in-house LIBS system was optimized to detect an Au standard through a process of line selection across acquisition delay times, followed by determining limit of detection (LOD). The optimized LIBS system was applied to Au-labeled Escherichia coli detection on a commercial LFIA; comparison with colorimetric detection yielded similar LODs (1.03E4 and 8.890E3 CFU/mL respectively). Optimization was repeated with lanthanide standards to determine if they were viable alternatives to Au labels. It was found that europium (Eu) and ytterbium (Yb) may be more favorable biomolecular labels than Au. To test whether Eu-complexed polymers conjugated to antibodies could be used as labels in LFIAs, the conjugates were successfully applied to E. coli detection in a modified commercial LFIA. The results suggest interesting opportunities for creating highly multiplexed LFIAs. Multiplexed, sensitive, portable, and rapid LIBS detection of biomolecules concentrated and labeled on LFIAs is highly relevant for applications like food safety, where in-field food contaminant detection is critical. Graphical abstract.