In a study with mice, researchers at the UCLA Jonsson Comprehensive Cancer Center have identified a new mechanism for delivering a drug that can help stop tumors from growing and keep cancer from recurring. The scientists found that they could reengineer adipocytes — fat cells that provide fatty acids with the energy needed for tumors to grow and spread — to reverse their role in tumor development and deliver cancer-fighting drugs directly to the area of the body immediately surrounding the tumor.
Although there have been many improvements over the past decade in treatment techniques for solid tumor cancers (which include immune-based therapies), cancer often recurs and it can be even more aggressive after therapy. To prevent cancer from recurring, drugs need to be delivered directly to the tumor.
The researchers theorized that because fat cells are plentiful in the human body and can be easily isolated and purified, they could potentially serve as an efficient drug delivery system. However, tumor cells cause fat cells to release the fatty acids that support tumor growth. To overcome that issue, the researchers added cancer-fighting drugs (doxorubicin) to the fat cells, making them function like Trojan horses once they reach the tumor.
The team tested the new drug delivery system by using UCLA-engineered fat cells to carry lipid-linked doxorubicin, a chemotherapy drug commonly used to treat cancer, and found the drug was able to successfully load into the lipid droplets consisting of an anticancer fatty acid within the fat cells. Linking the fat-soluble lipid molecule to doxorubicin can help reduce toxicity of the drug toward fat cells and enhance drug loading capability inside the fat cells. Once injected such fat cells into the tumor site or surgical site with residual tumor tissues, the encapsulated anticancer doxorubicin and fatty acid can be gradually released toward the tumor cells through lipid metabolism, subsequently inhibiting tumor growth and recurrence. Inside tumor cells, the lipid linked to doxorubicin can be effectively cleaved to show the killing effect of doxorubicin.
By utilizing fat cells with a therapeutic capsule, the team was able to demonstrate that the lipid metabolism pathway can be used to deliver drugs directly to solid tumors. The approach could not only be useful for delivering cancer drugs to tumors, but could potentially be applied to other lipid metabolism related diseases.
Reference: Wen, et al. (2019) Adipocytes as Anticancer Drug Delivery Depot. Matter. DOI: https://doi.org/10.1016/j.matt.2019.08.007
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