氨基化替菌酸衍生物是高效的核酸载体。之前我们证明配体官能化替菌酸衍生物在体外通过受体介导的内化显著增强了细胞类型特异性。本研究旨在改善替菌酸衍生物的生物相容性和肿瘤靶向效力，我们对腺苷功能化氨替菌酸衍生物进行了聚乙二醇化 (pAVC聚合物)。我们证实了pAVC聚合物携带siRNA进入肿瘤细胞的摄取过程是腺苷受体 (AR) 依赖的，并且该过程被AMP而非GMP特异性抑制。pAVC聚合物不仅保留了受体识别能力并且显著降低了细胞毒性，还在体内显示出了显著的肿瘤靶向效应。由siRNA (靶向STAT3) 和PEG置换程度最高的pAVC4聚合物制备的纳米粒子，高度特异性地将siRNA运送到肿瘤组织，沉默了STAT3并抑制了肿瘤生长。pAVC聚合物可能是用于肿瘤特异性运送核酸药物的一种有前景的载体。版权所有 © 2023. Elsevier B.V. 发行。

Aminated curdlan derivatives are highly effective nucleic acid carriers. Previously, we proved that the ligand-functionalized curdlan derivatives have greatly enhanced cell type specificity induced by receptor-mediated internalization in vitro. In this study, to improve biocompatibility and enhance tumor-targeting efficacy of the curdlan derivative, we pegylated the adenosine functionalized amino curdlan derivative (denoted by pAVC polymer). We confirmed that the uptake of pAVC polymer carrying siRNA by tumor cells was adenosine receptor (AR)-dependent and was specifically inhibited by AMP but not by GMP. The pAVC polymers not only preserved the receptor recognition and exhibited significantly decreased cytotoxicity but also showed remarkable tumor targeting efficiency in vivo. The nanoparticles formulated from siRNA (against STAT3) and pAVC4 polymer, which bears the highest degree of PEG substitution, delivered siRNA highly specifically to tumor tissue, knocked down STAT3, and inhibited tumor growth. The pAVC polymers may be a promising carrier for tumor specific delivery of nucleic acid drugs.Copyright © 2023. Published by Elsevier B.V.