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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. 

Abstract 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. 

Abstract Recent micro-CT scans have demonstrated a much larger magnetic nanoparticle distribution volume in tumors after localized heating than those without heating, suggesting possible heating-induced nanoparticle migration. In this study, a theoretical simulation was performed on tumors injected with magnetic nanoparticles to evaluate the extent to which the nanoparticle redistribution affects the temperature elevation and thermal dosage required to cause permanent thermal damage to PC3 tumors. 0.1 cc of a commercially available ferrofluid containing magnetic nanoparticles was injected directly to the center of PC3 tumors. The control group consisted of four PC3 tumors resected after the intratumoral injection, while the experimental group consisted of another four PC3 tumors injected with ferrofluid and resected after 25 min of local heating. The micro-CT scan generated tumor model was attached to a mouse body model. The blood perfusion rates in the mouse body and PC3 tumor were first extracted based on the experimental data of average mouse surface temperatures using an infrared camera. A previously determined relationship between nanoparticle concentration and nanoparticle-induced volumetric heat generation rate was implemented into the theoretical simulation. Simulation results showed that the average steady-state temperature elevation in the tumors of the control group is higher than that in the experimental group where the nanoparticles are more spreading from the tumor center to the tumor periphery (control group: 70.6±4.7 °C versus experimental group: 69.2±2.6 °C). Further, we assessed heating time needed to cause permanent thermal damage to the entire tumor, based on the nanoparticle distribution in each tumor. The more spreading of nanoparticles to tumor periphery in the experimental group resulted in a much longer heating time than that in the control group. The modified thermal damage model by Dr. John Pearce led to almost the same temperature elevation distribution; however, the required heating time was at least 24% shorter than that using the traditional Arrhenius integral, despite the initial time delay. The results from this study suggest that in future simulation, the heating time needed when considering dynamic nanoparticle migration during heating is probably between 19 and 29 min based on the Pearce model. In conclusion, the study demonstrates the importance of including dynamic nanoparticle spreading during heating and accurate thermal damage model into theoretical simulation of temperature elevations in tumors to determine thermal dosage needed in magnetic nanoparticle hyperthermia design. 

A Eulerian—Lagrangian model has been developed to simulate particle attachment to surfaces with arc-shaped ribs in a two-dimensional channel flow at low Reynolds numbers. Numerical simulation has been performed to improve the quantitative understanding of how rib geometries enhance shear rates and particle-surface interact for various particle sizes and flow velocities. The enhanced shear rate is attributed to the wavy flows that develop over the ribbed surface and the weak vortices that form between adjacent ribs. Varying pitch-to-height ratio can alter the amplitude of the wavy flow and the angle of attack of the fluid on the ribs. In the presence of these two competing factors, the rib geometry with a pitch-to-height ratio of two demonstrates the greatest shear rate and the lowest fraction of particle attachment. However, the ribbed surfaces have negligible effects on small particles at low velocities. A force analysis identifies a threshold shear rate to reduce particle attachment. The simulated particle distributions over the ribbed surfaces are highly non-uniform for larger particles at higher velocities. The understanding of the effect of surface topography on particle attachment will benefit the design of surface textures for mitigating particulate fouling in a wide range of applications.