Cancer Photodynamic Therapy by use of RES-avoiding Liposomes

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Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used such liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT.We also determined the liposomal trafficking by use of positron emission tomography. RES-avoinding liposomes havging long-circulating character, namely glucuronic acid-midified or PEG-modified liposomes, started to accumulate in tumor quite early after i.v. injection. Part of BPD-MA in liposomes, however, transfered to lipoproteins in the plasma, altought the liposomal formulation was useful for PDT.Therefore, liposomalization of BPD-MA should be investigated further for getting practical liposomal photosensitizer for clinical use.