More than just a fruit: Grapefruit-derived nanovectors deliver cancer drugs

Exosomes, cell-derived vesicles, have been shown to play key roles in many biological processes, including intercellular signaling, coagulation, and oncogenesis. Recently, there has been growing interest in exploring the use of exosomes as therapeutic delivery vehicles. Exosomes have been used to deliver small molecule therapeutics as well as targeted agents such as small interfering RNA. The advantages of exosomes as delivery vehicles include their native role in biological processes and their ability to deliver biologically derived agents such as nucleic acids and proteins. Some of the key challenges in translating exosomes for drug delivery include the scale of production and formulation of exosomes with desirable surface and trafficking properties. Wang et al. aimed to address these challenges by developing grapefruit-derived nanovectors (GNVs), exosome-like nanoparticles, as anticancer agents. The investigators previously reported that exosome-like nanoparticles can be generated from grapefruit plants in large quantities. In this study, they aimed to use the GNVs as drug delivery vehicles for the treatment of cancer. The investigators recognized that one key feature of tumors is inflammation and therefore hypothesized that GNVs with surfaces that resemble inflammatory cells can be trafficked preferentially to tumors. In this report, GNVs were coated with plasma membrane from activated leukocytes to create particles called IGNVs. The authors demonstrated that these IGNVs indeed home to sites of inflammation, and the homing effect is mediated by CXCR2 and LFA-1 cell-surface proteins. The investigators then loaded the IGNVs with doxorubicin and curcumin, two anticancer agents, and demonstrated that these drug-loaded IGNVs could delay tumor growth in mouse flank xenograft models of colon and breast cancer. This is innovative work, but clinical translation will be challenging. The proposed approach relies on coating the GNVs with plasma membrane from activated leukocytes, which will limit the scale of production. There is also the issue of immunogenicity if IGNVs are generated using leukocytes from sources other than the patient who will receive therapy. Future research on exosome-based drug delivery should focus on developing scalable methods to generate biocompatible exosomes. Q. Wang et al ., Grapefruit-derived nanovectors use an activated leukocyte trafficking pathway to deliver therapeutic agents to inflammatory tumor sites. Cancer Res . 10.1158/0008-5472.CAN-14-3095 (2015).[[Abstract]][1] [1]: http://cancerres.aacrjournals.org/content/early/2015/04/16/0008-5472.CAN-14-3095