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首页> 外文期刊>Biomaterials Science >Balancing polymer hydrophobicity for ligand presentation and siRNA delivery in dual function CXCR4 inhibiting polyplexes
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Balancing polymer hydrophobicity for ligand presentation and siRNA delivery in dual function CXCR4 inhibiting polyplexes

机译：平衡聚合物疏水性以实现双功能抑制CXCR4的多链体的配体呈递和siRNA递送

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In the present study, a series of copolymers (PAMD-Ch) was synthesized by grafting polymeric Plerixafor/AMD3100 (PAMD) with different amounts of cholesterol and the effect of cholesterol modification on siRNA delivery was investigated. PAMD-Ch/siRNA polyplexes exhibited improved colloidal and enzymatic stability when compared with PAMD/siRNA polyplexes containing no cholesterol. PAMD-Ch with low (17 wt%) and medium (25 wt%) cholesterol content exhibited CXCR4 antagonism comparable to unmodified PAMD. Cholesterol modification increased cell uptake of siRNA polyplexes and significantly decreased sensitivity of siRNA transfection to the presence of serum. When used to deliver anticancer siRNA against polo-like kinase 1 (PLK1), polyplexes based on PAMD-Ch with 17 wt% cholesterol exhibited the highest cancer cell killing activity both in serum-free and serum-containing conditions. Overall, the results of this study validate cholesterol modified PAMD as dual-function delivery vectors suitable for efficient delivery of anticancer siRNA and simultaneous CXCR4 inhibition for combined anticancer therapies.
机译：在本研究中，通过用不同量的胆固醇接枝聚合物Plerixafor / AMD3100（PAMD）合成了一系列共聚物（PAMD-Ch），并研究了胆固醇修饰对siRNA传递的影响。与不含胆固醇的PAMD / siRNA复合物相比，PAMD-Ch / siRNA复合物显示出改善的胶体和酶稳定性。具有低（17 wt％）和中等（25 wt％）胆固醇含量的PAMD-Ch表现出与未修饰PAMD相当的CXCR4拮抗作用。胆固醇修饰可增加siRNA复合物的细胞摄取，并显着降低siRNA转染对血清的敏感性。当用于递送针对polo样激酶1（PLK1）的抗癌siRNA时，基于PAMD-Ch的胆固醇含量为17 wt％的复合物在无血清和含血清条件下均表现出最高的癌细胞杀伤活性。总的来说，这项研究的结果证实了胆固醇修饰的PAMD是适合于有效递送抗癌siRNA和同时抑制CXCR4的双重功能递送载体，以用于联合抗癌治疗。

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