Nanoparticle Delivery in Prostate Tumors Implanted in Mice Facilitated by Either Local or Whole-Body Heating

This work discusses in vivo experiments that were performed to evaluate whether local or whole-body heating to 40 °C reduced interstitial fluid pressures (IFPs) and enhanced nanoparticle delivery to subcutaneous PC3 human prostate cancer xenograft tumors in mice. After heating, 0.2 mL of a previously developed nanofluid containing gold nanoparticles (10 mg Au/mL) was injected via the tail vein. The induced whole-body hyperthermia led to increases in tumor and mouse body blood perfusion rates of more than 50% and 25%, respectively, while the increases were much smaller in the local heating group. In the whole-body hyperthermia groups, the IFP reduction from the baseline at the tumor center immediately after heating was found to be statistically significant when compared to the control group. The 1 h of local heating group showed IFP reductions at the tumor center, while the IFPs increased in the periphery of the tumor. The intratumoral gold nanoparticle accumulation was quantified using inductively coupled plasma mass spectrometry (ICP-MS). Compared to the control group, 1 h or 4 h of experiencing whole-body hyperthermia resulted in an average increase of 51% or 67% in the gold deposition in tumors, respectively. In the 1 h of local heating group, the increase in the gold deposition was 34%. Our results suggest that 1 h of mild whole-body hyperthermia may be a cost-effective and readily implementable strategy for facilitating nanoparticle delivery to PC3 tumors in mice.

Mild Whole-Body Hyperthermia-Induced Interstitial Fluid Pressure Reduction and Enhanced Nanoparticle Delivery to PC3 Tumors: In Vivo Studies and Micro-Computed Tomography Analyses

In this study, we performed in vivo experiments on mice to evaluate whether whole-body hyperthermia enhances nanoparticle delivery to PC3 (prostatic cancer) tumors. PC3 xenograft tumors in immunodeficient mice were used in this study. The mice in the experimental group were subjected to whole-body hyperthermia by maintaining their body temperatures at 39–40 °C for 1 h. Interstitial fluid pressures (IFPs) in tumors were measured before heating, immediately after, and at 2 and 24 h postheating in both the experimental group and in a control group (without heating). A total of 0.2 ml of a newly developed nanofluid containing gold nanoparticles (AuNPs) was delivered via the tail vein in both groups. The micro-computed tomography (microCT) scanned images of the resected tumors were analyzed to visualize the nanoparticle distribution in the tumors and to quantify the total amount of nanoparticles delivered to the tumors. Statistically significant IFP reductions of 45% right after heating, 47% 2 h after heating, and 52% 24 h after heating were observed in the experimental group. Analyses of microCT scans of the resected tumors illustrated that nanoparticles were more concentrated near the tumor periphery rather than at the tumor center. The 1-h whole-body hyperthermia treatment resulted in more nanoparticles present in the tumor central region than that in the control group. The mass index calculated from the microCT scans suggested overall 42% more nanoparticle delivery in the experimental group than that in the control group. We conclude that 1-h mild whole-body hyperthermia leads to sustained reduction in tumoral IFPs and significantly increases the total amount of targeted gold nanoparticle deposition in PC3 tumors. The present study suggests that mild whole-body hyperthermia is a promising approach for enhancing targeted drug delivery to tumors.

Targeted removal of leukemia cells from the circulating system by whole-body magnetic hyperthermia in mice

Whole-body hyperthermia after intravenous injection of EpCAM antibody immobilized on magnetic nanoparticles (MNPs) decreased leukemia cells in AKR mice. Simulation analysis showed effective heat transfer from MNPs to leukemia cells.