Identifying Predictors of Nanoparticle Uptake in Cancer Cells

The delivery of drugs to target sites of disease in the body is hampered by rapid clearance, degradation, and off-target toxicity. Some drugs, such as chemotherapy agents, kill both the diseased and healthy cells making the drug toxic. Other drugs are unable to reach the site of interest with an effective dose. Nanoparticles are particles sized at the nanoscale level. It has been shown that these particles can be utilized as delivery systems to aid in drug therapy and diagnostics. Nanoparticle delivery systems are unique because they can be designed to control the tissues to which the drugs are delivered and the rate of drug release; thereby preventing off-target toxicity, rapid clearance and degradation, and ultimately increasing drug potency through efficient delivery to target tissues. Their surface materials can be functionalized with targeting peptides and outer layers which preferentially adhere to diseased cells. However, there still exist many challenges in designing nanoparticles that are taken up by cancer cells in sufficient amounts. While some cancer cell lines take up nanoparticles efficiently and some nanoparticles seem to be more easily taken up, it is not known exactly what factors primarily drive nanoparticle uptake.

Using a pooled cell line screening approach, called PRISM, we investigated the uptake of forty different nanoparticle formulations across five hundred different cancer cell lines. This allowed us to observe trends across a large data set and thus identify possible predictors of nanoparticle uptake in cancer cells. It was found that cancer cell lineage is not a major indicator of nanoparticle uptake level. Interestingly, however, nanoparticle core material seems to play a major role in determining nanoparticle uptake patterns and tended to be an even stronger predictor of nanoparticle uptake patterns than nanoparticle surface material. Understanding the mechanistic components governing nanoparticle uptake provides us with the information to revolutionize the design of future nanoparticle devices by allowing them to achieve more predictable and efficient uptake by cells, and ultimately, tissues. This enables drugs to reach potency levels which have previously not been possible, while also maintaining the lowest toxicity levels when treating diseases such as cancer, osteoporosis and other incurable diseases for which treatment remains limited.