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Intratumorally Injection of ROS Mixed Drug to Create a Coagulum as Cancer Therapeutics Drug Depot

Aim: To explore the nature of hydrogen peroxide at high dosage for denature-aggregation of tumor with drugs through aggregation in denatured tumor as a coagulum of drug depot for slow release and prolonged treatment effect of drug. Methods :Injection of oxidant mixed drug into tumor: 1) Preparation of two 5 mL of BLM-I131, one was diluted with 0.12 mL NS and 0.2 mL of Bleomycin (BLM) (0.2 m Ci =49.67 μg BLM) for tumor injection in control group; one was diluted with 0.12 mL of H2O2 (0.833 mg/mL) and 0.2 mL of BLM (0.2 m Ci=49.67 μg BLM) for tumor injection in experimental group; 2) Tumor imaging with BLM-I131 analyzed at different time points; 3) Radioactivity in tumor of mice analyzed under SPECT scanning imaging instrument at the 0, 5, 1, 2, 4, 8, 24, 48, 96, 120, 144 and 168 h time points. Activity of isotope I131 is representing the BLM retaining time in tumor; 4) Tumor sections was examined for cellular and extracellular matrix changes of histological structure. Results : It was observed that BLM-I131 with ROS in tumors sustained for 168 h while BLM-I131 with NS in tumors sustained for 8 h only. Radioactivity of BLM-I131 in tumors with ROS reached a peak in 1.5 h and second peak at 20 h and extended to 168 h in average, while radioactivity of BLM-I131 with NS reached the peak in 0.5 h, then decreased to 30% in 1.5 h and quickly to background in 8 h; We observed the extracellular matrix changes in experimental tumor while no changes in control tumor. Conclusion: A water soluble oxidant mixed with free drug can function as a biological scissors to chop tumor matrix, resulting in the denaturation of tumor matrix into coagulation for a drug depot. It was showmen that BLMI131 sustained in tumor for a long time; while oxidant plays an important role to punch holes on cell membrane and resulted in an enhanced permeabilization of drug and increased concentration of drug in cancer cells.

Author(s): Baofa Yu and Qiang Fu

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