Jun Shao

Date of Graduation


Document Type



Objective. To develop a targeting delivery system for lung cancer prevention and treatment using tumor cells as the drug carrier. Methods. Doxorubicin has been loaded into B16-F10 murine melanoma. This drug-loaded tumor cell system (DLTC) has been characterized, and its anticancer activity evaluated on C57BL/6J mice bearing pulmonary B16-F10 melanoma. Results. Up to 96 {dollar}\\rm\\mu g{dollar} of doxorubicin could be loaded into {dollar}10\\sp6{dollar} cells. The release of drug from the DLTC was both cell concentration and temperature dependent. Over a six-month storage at {dollar}\\rm 4\\sp\\circ C,{dollar} there was a 25% loss of intracellular drug and 8% loss of the carrier cells from the DLTC suspension in PBS. Compared with either free solution or DLTC using extensively trypsinized cells, the briefly trypsinized DLTC resulted in much higher lung drug deposit and lower liver and spleen drug distribution in mice. The lung drug deposit by different DLTCs was correlated with the density of {dollar}\\rm GM\\sb3,{dollar} one of the major surface adhesion molecules on B16-F10. In vitro anti-proliferation study showed no difference of the activity between the DLTC and free solution. In metastasis prevention experiment, the animals were iv inoculated with {dollar}5\imes 10\\sp5{dollar} live B16-F10 cells on day 1, and then received daily iv treatment of either PBS (Group A), or 25 {dollar}\\rm\\mu g{dollar} drug in free solution (Group B) or in DLTC (Group C) on days 1-3. The lung metastases on day 14 were 554 (354-640), 214 (119-349) and 4 (3-5) for Group A, B, and C, respectively. In metastasis treatment experiment, the daily treatment was given on days 6-10, and the lung metastases on day 17 were 199 (104-269), 140 (62-208) and 29 (7-48) for Group A, B, and C, respectively. Results of single dose treatment on either day 1, 2, 3 or 4 indicated that the anticancer activity of DLTC was dosing-time dependent. Conclusions. DLTC, a lung targeting drug delivery system, has been developed. The surface adhesion molecules play an important role in the targeting activity. DLTC has demonstrated a high efficiency in lung metastasis prevention and treatment in animal models with B16-F10 melanoma.