tirapazamine and pheophorbide-a

In combination therapy, synergetic effects of drugs and their efficient delivery are essential. Herein, we screened 12 anticancer drugs for combination with photodynamic therapy (PDT) using pheophorbide a (Pba). On the basis of combination index (CI) values in cell viability tests, we selected tirapazamine (TPZ) and developed self-assembled gelatin nanoparticles (NPs) containing both Pba and TPZ. The resulting TPZ-Pba-NPs showed a synergetic effect to kill tumor cells because TPZ was activated under the hypoxic conditions that originated from the PDT with Pba and laser irradiation. After they were injected into tumor-bearing mice via the tail vein, TPZ-Pba-NPs showed 3.17-fold higher blood concentration and 4.12-fold higher accumulation in tumor tissue 3 and 24 h postinjection, respectively. Upon laser irradiation to tumor tissue, TPZ-Pba-NPs successfully suppressed tumor growth by efficient drug delivery and synergetic effects

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chlorophyll; Drug Carriers; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy; Gelatin; Light; Mice, Inbred C3H; Nanoparticles; Neoplasms; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Tirapazamine