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Updated: Feb 17, 2026
Kupffer Cell Isolation for Nanoparticle Toxicity Testing
Published on: August 18, 2015
Effect of removing Kupffer cells on nanoparticle tumor delivery
Anthony J Tavares1,2, Wilson Poon1,2, Yi-Nan Zhang1,2
1Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Abstract:
A recent metaanalysis shows that 0.7% of nanoparticles are delivered to solid tumors. This low delivery efficiency has major implications in the translation of cancer nanomedicines, as most of the nanomedicines are sequestered by nontumor cells. To improve the delivery efficiency, there is a need to investigate the quantitative contribution of each organ in blocking the transport of nanoparticles to solid tumors. Here, we hypothesize that the removal of the liver macrophages, cells that have been reported to take up the largest amount of circulating nanoparticles, would lead to a significant increase in the nanoparticle delivery efficiency to solid tumors. We were surprised to discover that the maximum achievable delivery efficiency was only 2%. In our analysis, there was a clear correlation between particle design, chemical composition, macrophage depletion, tumor pathophysiology, and tumor delivery efficiency. In many cases, we observed an 18-150 times greater delivery efficiency, but we were not able to achieve a delivery efficiency higher than 2%. The results suggest the need to look deeper at other organs such as the spleen, lymph nodes, and tumor in mediating the delivery process. Systematically mapping the contribution of each organ quantitatively will allow us to pinpoint the cause of the low tumor delivery efficiency. This, in effect, enables the generation of a rational strategy to improve the delivery efficiency of nanoparticles to solid tumors either through the engineering of multifunctional nanosystems or through manipulation of biological barriers.
Insights
Improving nanoparticle delivery to solid tumors is crucial for cancer nanomedicines. While removing liver macrophages increased delivery 18-150 times, the maximum efficiency remained low at 2%.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Nanoparticle delivery to solid tumors is inefficient (0.7%), hindering cancer nanomedicine translation.
- Most nanomedicines are sequestered by non-tumor cells, necessitating investigation into transport barriers.
Purpose of the Study:
- To investigate the quantitative contribution of organs in blocking nanoparticle transport to solid tumors.
- To test the hypothesis that removing liver macrophages enhances nanoparticle delivery efficiency.
Main Methods:
- Hypothesized that liver macrophage depletion would increase nanoparticle delivery.
- Analyzed correlations between particle design, composition, macrophage depletion, tumor pathophysiology, and delivery efficiency.
Main Results:
- Liver macrophage depletion increased delivery efficiency 18-150 times in some cases.
- Maximum achievable nanoparticle delivery efficiency to solid tumors was unexpectedly limited to 2%.
Conclusions:
- Liver macrophages are not the sole factor limiting nanoparticle delivery to tumors.
- Further investigation into spleen, lymph nodes, and tumor contributions is needed.
- Quantitative mapping of organ contributions is essential for developing strategies to enhance nanoparticle delivery.
