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

Abstract

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.

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

“…Using the same in vivo model of breast cancer as in the present work, we recently showed that gold nanoparticles transiently increased the volume of blood vessels in tumor tissue after both intragastrical and intravenous administration [ 30 ]. In order to check if a similar effect can be induced by AgNPs, we performed an analysis of the volume of blood vessels in tumor tissue after AgNPs treatment.…”

“…Another interesting aspect analyzed during the present study was the volume of blood vessels in tumor tissue after AgNPs administration. In our recent work using the same experimental model, we showed that gold nanoparticles induce transient vasodilation in tumor tissue after both intragastric and intravenous administration [ 30 ]. In the present study, we did not observe such an effect, which proved that the vasodilating effect was specific to gold nanoparticles.…”

Long-Term Accumulation, Biological Effects and Toxicity of BSA-Coated Gold Nanoparticles in the Mouse Liver, Spleen, and Kidneys

“…This is in line with the recent data showing that 1 mg/kg AuNPs might be around the real therapeutical dose. 25 , 36 , 37 BSA-AuNPs are considered a safe platform among various AuNPs types, nevertheless, their biocompatibility still needs to be carefully assessed. In one of the recent publications, five different doses of AuNPs coated with BSA ranging from 1.16 mg/kg to 5.84 mg/kg were tested for 8 consecutive days after intravenous injections in mice.…”

Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation

“…The nanomaterial surface may also contain structural defects inducing the formation of reactive groups [36], as well as transition metals that can generate ROS by Fenton and Haber-Weiss type reactions [37]. In addition, environmental oxidants such as ozone, semiquinones, and NO can adsorb to the nanomaterial surface and enter cells through the so-called "Trojan horse effect" [37]. Nanomaterials may also indirectly enable the production of ROS by triggering cellular mechanisms.…”