Li Manhong, Li Yong, Huang Xiaohui, Lu Xizhi
a Department of Pathology , The First Affiliated Hospital of Shantou University Medical College , Shantou 515041 , China.
J Biomater Sci Polym Ed. 2015;26(13):813-27. doi: 10.1080/09205063.2015.1057991. Epub 2015 Jul 13.
Captopril-polyethyleneimine (CP) containing low molecular weight polyethyleneimine and anti-angiogenesis drug captopril conjugated via an amide bond was fabricated to modify gold nanoparticles and complex with siRNA to construct siRNA/CP/GNP complexes for the co-delivery of drug and siRNA in anti-angiogenesis breast cancer therapy. The self-assembled siRNA/CP/GNP complexes exhibited desirable and homogenous particle size, reasonable positive charges and condensation ability, and effective gene-silencing property in vitro. In addition, siRNA/CP/GNP complexes co-delivering captopril and siRNA achieved combined angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor mRNA and protein via different pathways in vitro, as compared to mono-delivery systems. In vivo investigation on nude mice bearing MDA-MB435 tumor xenografts revealed that siRNA/CP/GNP complexes possessed satisfying tumor homing ability and strong antitumor activity. These findings suggested that siRNA/CP/GNP complexes could be an ideal system for simultaneous transfer of drug and siRNA, which might be a new promising strategy for effective breast cancer therapy.
制备了含有低分子量聚乙烯亚胺和通过酰胺键与抗血管生成药物卡托普利共轭的卡托普利-聚乙烯亚胺（CP），用于修饰金纳米颗粒并与siRNA复合，构建siRNA/CP/GNP复合物，用于在抗血管生成乳腺癌治疗中共同递送药物和siRNA。自组装的siRNA/CP/GNP复合物在体外表现出理想且均匀的粒径、合理的正电荷和凝聚能力以及有效的基因沉默特性。此外，与单递送系统相比，共同递送卡托普利和siRNA的siRNA/CP/GNP复合物通过在体外不同途径更有效地下调血管内皮生长因子mRNA和蛋白质的表达，实现了联合血管生成抑制。对携带MDA-MB435肿瘤异种移植物的裸鼠进行的体内研究表明，siRNA/CP/GNP复合物具有令人满意的肿瘤归巢能力和强大的抗肿瘤活性。这些发现表明，siRNA/CP/GNP复合物可能是药物和siRNA同时转移的理想系统，这可能是有效乳腺癌治疗的一种新的有前景的策略。
