Comb-Like Amphiphilic Polycarbonates with Different Lengths of Cationic Branches for Enhanced siRNA Delivery.,Macromolecular Bioscience

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Comb-Like Amphiphilic Polycarbonates with Different Lengths of Cationic Branches for Enhanced siRNA Delivery.
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2020-05-13 , DOI: 10.1002/mabi.202000143
Yanliang Dong ₁ , Junhui Zhou ₂ , Changrong Wang ₁ , Yaping Wang _{1,

3} , Liandong Deng ₁ , Jianhua Zhang ₁ , Anjie Dong _{1,

3}

Affiliation

Owing to the biodegradability and good biocompatibility polycarbonates show the versatile class of applications in biomedical fields. While their poor functional ability seriously limited the development of functional polycarbonates. Herein, a new Br‐containing cyclic carbonate (MTC‐Br) and a polycarbonate atom transfer radical polymerization (ATRP) macro‐initiator (PEG‐PMTC‐Br) is synthesized. Then, by initiating the side‐chain ATRP of 2‐(dimethyl amino)ethyl methacrylate (DMAEMA) on PEG‐PMTC‐Br, a series of comb‐like amphiphilic cationic polycarbonates, PEG‐b‐(PMTC‐g‐PDMAEMA) (GMDMs), with different lengths of cationic branches are successfully prepared. All these poly(ethylene glycol)‐b‐(poly((5‐methyl‐2‐oxo‐1,3‐dioxane‐5‐yl) methyl 2‐bromo‐2‐methylpropanoate/1,3‐dioxane‐2‐one)‐g‐poly(2‐dimethyl aminoethyl methacrylate) (GMDMs) self‐assembled nanoparticles (NPs) (≈180 nm, +40 mV) can well bind siRNA to form GMDM/siRNA NPs. The gene silence efficiency of GMDM/siRNA high to 80%, which is even higher than the commercial transfection reagent lipo2000 (76%). But GMDM/siRNA shows lower cell uptake than lipo2000. So, the high gene silence ability of GMDM/siRNA NPs can be attributed to the strong intracellular siRNA trafficking capacity. Therefore, GMDM NPs are potential siRNA vectors and the successful preparation of comb‐like polycarbonates also provides a facile way for diverse side‐chain functional polycarbonates, expanding the application of polycarbonates.

中文翻译：

具有不同长度阳离子分支的梳状两亲聚碳酸酯可增强siRNA的传递。

由于其可生物降解性和良好的生物相容性，聚碳酸酯在生物医学领域显示出多种用途。尽管它们差的功能能力严重限制了功能聚碳酸酯的开发。本文合成了一种新的含溴环状碳酸酯（MTC-Br）和聚碳酸酯原子转移自由基聚合（ATRP）宏观引发剂（PEG-PMTC-Br）。然后，通过在PEG-PMTC-Br上引发甲基丙烯酸2-（二甲基氨基）乙酯（DMAEMA）的侧链ATRP，得到一系列梳状两亲阳离子聚碳酸酯PEG-b-（PMTC-g-PDMAEMA）（已成功制备了具有不同长度阳离子分支的GMDM）。所有这些聚（乙二醇）-b-（聚（（5-甲基-2-氧代-1,3-二恶烷-5-基）甲基2-溴-2-甲基丙酸酯/ 1，自组装的纳米颗粒（NPs）（≈180nm，+40 mV）（3-二恶烷-2-一）-g-聚（甲基丙烯酸2-二甲基氨基乙基酯）（GMDMs）可以很好地结合siRNA形成GMDM / siRNA NPs。GMDM / siRNA的基因沉默效率高达80％，甚至高于商业转染试剂lipo2000（76％）。但是GMDM / siRNA的细胞摄取低于lipo2000。因此，GMDM / siRNA NPs的高基因沉默能力可以归因于强大的细胞内siRNA转运能力。因此，GMDM NP是潜在的siRNA载体，成功制备梳状聚碳酸酯也为各种侧链功能聚碳酸酯提供了简便的方法，从而扩大了聚碳酸酯的应用范围。甚至比商业转染试剂lipo2000（76％）高。但是GMDM / siRNA的细胞摄取低于lipo2000。因此，GMDM / siRNA NPs的高基因沉默能力可以归因于强大的细胞内siRNA转运能力。因此，GMDM NP是潜在的siRNA载体，成功制备梳状聚碳酸酯也为各种侧链功能聚碳酸酯提供了简便的方法，从而扩大了聚碳酸酯的应用范围。甚至比商业转染试剂lipo2000（76％）高。但是GMDM / siRNA的细胞摄取低于lipo2000。因此，GMDM / siRNA NPs的高基因沉默能力可以归因于强大的细胞内siRNA转运能力。因此，GMDM NP是潜在的siRNA载体，成功制备梳状聚碳酸酯也为各种侧链功能聚碳酸酯提供了简便的方法，从而扩展了聚碳酸酯的应用范围。

更新日期：2020-05-13

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