一种Legumain响应释放阿霉素缓释纳米制剂及制备方法与作为制备载体药物的应用,本发明利用肿瘤组织高表达Legumain的生物学特性,制备Legumain响应的纳米水凝胶,从而实现对肿瘤组织的双重靶向效应(主动靶向和被动靶向),减少阿霉素对正常组织的次生伤害,本发明以透明质酸作为阿霉素药物载体的基础材料,透明质酸广泛存在与生物体的正常组织中,相对其他外源材料,具有较高的生物相容性和安全性,肿瘤组织还高表达透明质酸受体,因此以透明质酸作为载体材料,还能进一步达到靶向的效果。

Legumain is an asparaginyl endopeptidase that is highly up-regulated in a number of solid tumours. The aim of this work was to prepare a novel hyaluronic acid (HA) based legumain sensitive nanogel for the delivery of doxorubicin with a high targeting efficiency both in vitro and in vivo. The legumain sensitive property is achieved by the conjugation of doxorubicin with HA via a legumain substrate peptide bridge. This HA derivative is further crosslinked in a water/oil solvent system to form a polygonal nanogel. The developed nanogel exhibited an improved tumour inhibition effects and reduced system toxicity in a lung cancer mice model.