Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea.
ACS Biomater Sci Eng. 2020 Jan 13;6(1):494-504. doi: 10.1021/acsbiomaterials.9b01724. Epub 2019 Dec 27.
Branched polymers as drug delivery carriers have been widely attempted due to their outstanding drug loading capability and complex stability like branched polyethyleneimine (B-PEI). However, branched polymers without biodegradability may cause toxicity as they can accumulate in the body. Herein, we report branched modified nona-arginine (B-mR9) composed of redox-cleavable disulfide bonds to form stable complexes with methotrexate (MTX) as an anticancer agent, which is further coated with hyaluronic acid (HA). The HA-coated nanoparticles provide targetability for the CD44 cell surface receptor. The B-mR9-MTX/HA can effectively aid in intracellular MTX delivery to CD44 overexpressing cancer cells being degradable by the reducing environments of the cancer cells. The B-mR9-MTX/HA exhibits not only a glutathione-triggered degradability but also an outstanding CD44-mediated MTX delivery efficacy. In addition, its superior tumor inhibition capability was confirmed through an in vivo study. The results suggest that the HA-coated B-mR9 nanoparticle can be used as a drug delivery platform.
支链聚合物因其出色的载药能力和复杂稳定性（如支化聚乙烯亚胺（B-PEI））而被广泛尝试作为药物传递载体。然而，没有生物降解性的支链聚合物可能会因其在体内积累而产生毒性。在这里，我们报告了由氧化还原可裂解二硫键组成的支化修饰的九聚精氨酸（B-mR9），以形成与甲氨蝶呤（MTX）作为抗癌药物的稳定复合物，进一步用透明质酸（HA）包被。HA 包被的纳米颗粒为 CD44 细胞表面受体提供靶向性。B-mR9-MTX/HA 可以有效地帮助细胞内 MTX 递送至过表达 CD44 的癌细胞，并且可被癌细胞的还原环境降解。B-mR9-MTX/HA 不仅表现出谷胱甘肽触发的降解性，而且还表现出出色的 CD44 介导的 MTX 递药功效。此外，通过体内研究证实了其优异的肿瘤抑制能力。结果表明，HA 包被的 B-mR9 纳米颗粒可用作药物传递平台。
