用于增强基因传递的超支化聚（β-氨基酯）s (HPAEs) 结构优化：非理想终止消除,Nanomaterials

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用于增强基因传递的超支化聚（β-氨基酯）s (HPAEs) 结构优化：非理想终止消除
Nanomaterials ( IF 4.4 ) Pub Date : 2022-11-04 , DOI: 10.3390/nano12213892
Yinghao Li ₁ , Zhonglei He _{1,

2} , Jing Lyu ₁ , Xianqing Wang ₁ , Bei Qiu ₁ , Irene Lara-Sáez ₁ , Jing Zhang ₃ , Ming Zeng ₄ , Qian Xu ₁ , Sigen A ₁ , James F Curtin _{2,

5} , Wenxin Wang ₁

Affiliation

许多具有超分支结构的聚合基因递送纳米载体已被证明优于其线性对应物。更高的递送效率通常归因于支化聚合物丰富的末端基团，它们在货物截留、材料-细胞相互作用和核内体逃逸中起着关键作用。超支化聚（β-氨基酯）（HPAE）已发展成为一类安全高效的基因递送载体。尽管已经进行了大量研究来优化用于基因传递的 HPAE 结构，但仲胺残基对其主链单体的影响（被认为是非理想的终止）从未得到优化。在这项工作中，仔细评估了非理想终止的影响。而且，通过调整主链合成策略，合成了一系列仅具有理想末端的HPAEs，以进一步探索超支化结构的优点。通过 NMR 确定，与传统方法相比，通过改进的合成方法获得的 HPAE 显示出两倍以上的理想端基数量。它们的转染性能显着提高，在本研究中开发的最佳 HPAE 候选物优于领先的 DNA 递送商业基准，包括 Lipofectamine 3000、jetPEI 和 jetOPTIMUS。

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Hyperbranched Poly(β-amino ester)s (HPAEs) Structure Optimisation for Enhanced Gene Delivery: Non-Ideal Termination Elimination

Many polymeric gene delivery nano-vectors with hyperbranched structures have been demonstrated to be superior to their linear counterparts. The higher delivery efficacy is commonly attributed to the abundant terminal groups of branched polymers, which play critical roles in cargo entrapment, material-cell interaction, and endosome escape. Hyperbranched poly(β-amino ester)s (HPAEs) have developed as a class of safe and efficient gene delivery vectors. Although numerous research has been conducted to optimise the HPAE structure for gene delivery, the effect of the secondary amine residue on its backbone monomer, which is considered the non-ideal termination, has never been optimised. In this work, the effect of the non-ideal termination was carefully evaluated. Moreover, a series of HPAEs with only ideal terminations were synthesised by adjusting the backbone synthesis strategy to further explore the merits of hyperbranched structures. The HPAE obtained from modified synthesis methods exhibited more than twice the amounts of the ideal terminal groups compared to the conventional ones, determined by NMR. Their transfection performance enhanced significantly, where the optimal HPAE candidates developed in this study outperformed leading commercial benchmarks for DNA delivery, including Lipofectamine 3000, jetPEI, and jetOPTIMUS.

更新日期：2022-11-04

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