Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 106, Taiwan, R.O.C.
Advanced Membrane Materials Research Center, National Taiwan University of Science and Technology, Taipei, 106, Taiwan, R.O.C.
Macromol Biosci. 2019 May;19(5):e1800409. doi: 10.1002/mabi.201800409. Epub 2019 Mar 1.
Metastasis is a pathogenic spread of cancer cells from the primary site to surrounding tissues and distant organs, making it one of the primary challenges for effective cancer treatment and the major cause of cancer mortality. Heparin-based biomaterials exhibit significant inhibition of cancer cell metastasis. In this study, a non-anticoagulate heparin prodrug is developed for metastasis treatment with a localized treatment system using temperature sensitive, injectable, and biodegradable (poly-(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) polymeric hydrogel. The drug molecule (heparin) is conjugated with the polymer via esterification, and its sustained release is ensured by hydrolysis and polymeric biodegradation. An aqueous solution of the polymer could be used as an injectable solution at below 25 °C and it achieves gel formation at 37 °C. The anti-metastasis effect of the hydrogels is investigated both in vitro and in vivo. The results demonstrated that local administration of injectable heparin-loaded hydrogels effectively promote an inhibitory effect on cancer metastasis.
转移是癌细胞从原发性肿瘤扩散到周围组织和远处器官的一种致病过程，是有效治疗癌症的主要挑战之一，也是癌症死亡的主要原因。基于肝素的生物材料对癌细胞转移具有显著的抑制作用。在这项研究中，我们开发了一种非抗凝肝素前药，用于通过局部治疗系统治疗转移，该系统使用温度敏感、可注射和可生物降解的（聚（ε-己内酯-共-乳酸）-b-聚（乙二醇）-b-聚（ε-己内酯-共-乳酸））聚合物水凝胶。药物分子（肝素）通过酯化与聚合物连接，其通过水解和聚合物生物降解确保持续释放。聚合物的水溶液在低于 25°C 时可用作可注射溶液，在 37°C 时达到凝胶形成。我们在体外和体内研究了水凝胶的抗转移作用。结果表明，局部给予可注射的载肝素水凝胶可有效促进对癌症转移的抑制作用。
