Unknown

Dataset Information

0

Effect of removing Kupffer cells on nanoparticle tumor delivery.


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.

SUBMITTER: Tavares AJ 

PROVIDER: S-EPMC5754793 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Effect of removing Kupffer cells on nanoparticle tumor delivery.

Tavares Anthony J AJ   Poon Wilson W   Zhang Yi-Nan YN   Dai Qin Q   Besla Rickvinder R   Ding Ding D   Ouyang Ben B   Li Angela A   Chen Juan J   Zheng Gang G   Robbins Clinton C   Chan Warren C W WCW  

Proceedings of the National Academy of Sciences of the United States of America 20171205 51


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 bee  ...[more]

Similar Datasets

| S-EPMC7032111 | biostudies-literature
| S-EPMC5609780 | biostudies-literature
| S-EPMC6506271 | biostudies-literature
| S-EPMC11225973 | biostudies-literature
| S-EPMC10611415 | biostudies-literature
| S-EPMC4692542 | biostudies-other
| S-EPMC6402396 | biostudies-literature
| S-EPMC2453735 | biostudies-literature
| S-EPMC7439617 | biostudies-literature
| S-EPMC7072816 | biostudies-literature