Targeted delivery of chemotherapeutic drugs to tumor sites is a major challenge in cancer chemotherapy. Cell-based vectorization of therapeutic agents has great potential for cancer therapy in that it can target and maintain an elevated concentration of therapeutic agents at the tumor site and prevent their spread into healthy tissue. The use of circulating cells such as monocytes/macrophages (Ma) offers several advantages compared to nanoparticles as targeted drug delivery vehicles. Ma can be easily obtained from the patient, loaded in vitro with drugs and reinjected into the blood stream. Ma can selectively cross the partially compromised blood-brain barrier surrounding brain tumors and are known to actively migrate to tumors, drawn by chemotactic factors, including hypoxic regions where conventional chemo and radiation therapy are least effective. The utility of Ma as targeted drug delivery vehicles for photochemical internalization (PCI) of tumors was investigated in this study.
In vitro studies were conducted using a mixture of F98 rat glioma cells and rat macrophages loaded with a variety of chemotherapeutic agents including bleomycin and 5-fluorouracil. Preliminary data show that macrophages are resistant to both chemotherapeutics while significant toxicity is observed for F98 cells exposed to both drugs. Co-incubation of F98 cells with loaded Ma results in significant F98 toxicity suggesting that Ma are releasing the drugs and, hence providing the rationale for their use as delivery vectors for cancer therapies such as PCI.
Steen J. Madsen, Jonathan Gonzalez, Stephanie Molina, Rohit Kumar Nair, and Henry Hirschberg, "Macrophages as drug delivery vehicles for photochemical internalization (Conference Presentation)," Proc. SPIE 10050, Clinical and Translational Neurophotonics, 100500F (Presented at SPIE BiOS: January 28, 2017; Published: 19 April 2017); https://doi.org/10.1117/12.2253238.5370387592001.
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