Macrophage-mediated drug delivery system has emerged and gained wide interest as a novel strategy for cancer treatment. Among them, RAW264.7 cell was commonly used as the macrophage model for antitumor drug loading and delivery. However, this cell line was a macrophage-like cancerous cell with both immunogenicity and pro-tumorigenic properties, which may interfere with the positive response of the host immune system to developed tumor. Thus, the safety and efficacy of the RAW264.7 cell line as a drug carrier for cancer therapy remain questionable. Here, we constructed doxorubicin-loaded RAW264.7 cells and examined its antitumor efficacy in S180 tumor-bearing mice. The bio-distribution of RAW264.7 cells was determined by in vivo imaging technique, showing a high accumulation level of RAW264.7 cells in mice livers, spleens, and thymuses. A phenomenon of accelerated tumor growth was observed in mice treated with doxorubicin-loaded RAW264.7 cells. Thereafter, the effect of frequency, dose, and viability of injected RAW264.7 cells on S180 tumor growth was further investigated. The underlying mechanism was confirmed, attributing to the immune tolerance induced by excessive RAW264.7 cells. Our findings emphasized the latent limitation of RAW264.7 cells as drug carrier in current researches, and provided an experimental basis for the clinical safety of cell-mediated drug delivery system.
Keywords: Cell-mediated drug delivery system; Doxorubicin; Immune tolerance; RAW264.7 cell.