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Abstract 2152: A novel glycan targeting cancer therapy using lectin modified liposome

Introduction: Since the most outer layer of cancer cells is covered with various glycans, it would be one of the most effective targets in cancer therapy. We had previously discovered the specific fucosylated glycan in pancreatic cancer and a lectin, a protein specifically binds to glycan, named “rBC2LCN” could well worked as targeting bullet (Shimomura O, Oda T, et al: Mol Cancer Ther 2018). In this study, we applied this lectin as booster bullet of anticancer nanoparticles. We originally developed a novel glycan targeting anti-pancreatic cancer nanoparticles, namely Lectin-Dox, by modifying the surface of doxorubicin encapsulating PEGylated liposome (Dox) by rBC2LCN and verified the booster anti-tumor effects of the novel agent. Material and Methods: Lectin-Dox was prepared by the post insertion method (Ishida T, et al: FEBS Lett. 1999) from ready-made Dox using lipid linker. Experiment 1: Lectin-Dox and Dox were applied to two pancreatic cancer cell lines (Capan-1 and SUIT-2) which possess different binding affinity to rBC2LCN, thereafter the signal intensities were compared by fluorescent microscopy and flow cytometry to evaluate cellular bindings and uptakes. Experiment 2: To compare cytotoxicity in vitro of each solution, the 50% inhibitory concentration (IC50) against each cell lines were calculated. Experiment 3: Anti-tumor effects in vivo were evaluated using subcutaneous tumor bearing mouse derived from each cell lines. The solutions was injected via tail vein twice per week for 3 consecutive weeks, then tumor volumes and weights were compared. Results:Experiment 1: Cellular bindings and uptakes were both significantly stronger in Lectin-Dox group against Capan-1 (P Conclusions: Modifying the liposomal surface by the rBC2LCN improved it’s accumulation to the pancreatic cancer as demonstrated stronger anti-tumor effect. We regard this lectin could work as effective cancer targeting bullets, not only for small molecular drugs but also as surface decorator of nanoparticle drugs. Citation Format: Sota Kimura, Tatsuya Oda, Osamu Shimomura, Ko Kurimori, Tomoaki Furuta, Yoshihiro Miyazaki, Yang Yu, Jun Hirabayashi, Hiroaki Tateno. A novel glycan targeting cancer therapy using lectin modified liposome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2152.