Purpose: In order to improve side effects in oncological photodynamic therapy (PDT), it is necessary to reduce the dose and increase drug concentrations in a tumor concerned. Therefore, we attempted to develop a new drug delivery system (DDS) with the use of Poly(2-methacryloyloxyethyl phosphorylcholine (MPC)- co-n-butyl methacrylate-co-p-nitrophenylcarbonyloxyethyl methacrylate) (PMBN). Background: PDT of cancer is a noninvasive optical therapeutic method in which the topical or systemic delivery of photosensitizing durgs is followed by irradiation with broadband red light. Photosensitizers such as hematoporphyrin derivatives, Photofrin and Levulan have been used exclusively. However, these compounds have low localization for tumor by passive effect which cause low photodynamic effect and high skin photosensitivity. Therfore, the compounds with high selectivity for tumors, more adequate for PDT, is necessary. On the other hand, the water-soluble MPC polymer, an unit of PMBN, has been invented for more than 10years and widely used as approved safe and stable medical material. The PMBN we used in this study has the following characteristics: (1) the hydrophobic unit binds to hydrophobic material such as Verteporfin while the hydrophilic unit sustains water-solubility; (2) the polymer can bind to protein through the active ester; (3) it positively accumulates in cancerous lesions by means of antigen-antibody reactions or ligand-receptor reactions. Methods: BALB/cAJcl nu/nu bearing the human squamous cancer cells(1×107) were intravenously injected 6 mg/kg Verteporfin-PMBN preparation when the tumors grew to about 5 mm. Tissues were serially obtained at various times to measure tissue concentrations of Verteporfin. The tumor was irradiated then therapeutic effects were measured in three animal groups: group A, anti-EGFR antibody-Verteporfin-PMBN; group B, Verteporfin-PMBN (without antibody); and group N, negative control. Results: The anti-EGFR antibody-Verteporfin-PMBN accumulated at cancerous lesions more than 5 times compared to without antibody at 1 hour and the high concentration was remained until 24 hour and over. Regarding therapeutic effects, the tumors in group A were reduced in size as much as 10 times compared to group N and 6 times compared to group B. Discussion: Our polymer is characterized by the preservation of water solubility while binding to hydrophobic substances and the capability to bind to antibodies as well as ligands. Selective increased accumulation of the polymer leads to a reduction of its dose, which in turn reduces the incidence of photocytotoxic effect. The anti-EGFR antibody-Verteporfin-PMBN showed active enhancement effect regard to accumulation of photosensitizer intravenously and therapeutic effect, so that its application to DDS is very promising in oncological PDT.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 626.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO