BACKGROUND: The folate receptor (FR) is amplified in a wide variety of human tumors. Thus, targeting cytotoxic therapies to FR is a promising strategy for chemotherapy. MATERIALS AND METHODS: FR-targeted liposomal daunorubicin (f-L-DNR) was compared to non-targeted liposomal DNR (L-DNR) for cellular uptake and cytotoxicity in FR-expressing cells. Liposomal DNR retention was evaluated for liposomes loaded with either sodium citrate or ammonium sulfate as the trapping agent. The cellular uptake of liposomal DNR was determined by flow cytometry and fluorometry measurements while cytotoxicity was determined by the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Liposomal DNR retention was superior for liposomes prepared using ammonium sulfate. Cellular uptake of f-L-DNR in KB oral carcinoma cells, Chinese hamster ovary (CHO-FR-beta), and KG-1 human acute myelogenous leukemia cells were 9.4, 40, and 4,6-fold higher than non-targeted L-DNR, respectively. The cytotoxicity of f-L-DNR in KB and CHO-FR-beta cells was 18 times and 49 times higher than L-DNR, respectively. Both cellular uptake and cytotoxicity of f-L-DNR could be inhibited by 1 mM folic acid. CONCLUSION: FR-mediated delivery of liposomal DNR to FR-expressing cells increases DNR cellular uptake and cytotoxicity. Therefore, therapeutic evaluation in relevant animal models is warranted.
BACKGROUND: The folate receptor (FR) is amplified in a wide variety of humantumors. Thus, targeting cytotoxic therapies to FR is a promising strategy for chemotherapy. MATERIALS AND METHODS:FR-targeted liposomal daunorubicin (f-L-DNR) was compared to non-targeted liposomal DNR (L-DNR) for cellular uptake and cytotoxicity in FR-expressing cells. Liposomal DNR retention was evaluated for liposomes loaded with either sodium citrate or ammonium sulfate as the trapping agent. The cellular uptake of liposomal DNR was determined by flow cytometry and fluorometry measurements while cytotoxicity was determined by the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Liposomal DNR retention was superior for liposomes prepared using ammonium sulfate. Cellular uptake of f-L-DNR in KB oral carcinoma cells, Chinese hamster ovary (CHO-FR-beta), and KG-1 human acute myelogenous leukemia cells were 9.4, 40, and 4,6-fold higher than non-targeted L-DNR, respectively. The cytotoxicity of f-L-DNR in KB and CHO-FR-beta cells was 18 times and 49 times higher than L-DNR, respectively. Both cellular uptake and cytotoxicity of f-L-DNR could be inhibited by 1 mM folic acid. CONCLUSION:FR-mediated delivery of liposomal DNR to FR-expressing cells increases DNR cellular uptake and cytotoxicity. Therefore, therapeutic evaluation in relevant animal models is warranted.