Synthesis and Characterization of Click Nucleic Acid Conjugated Polymeric Microparticles for DNA Delivery Applications.
Synthesis and Characterization of Click Nucleic Acid Conjugated Polymeric Microparticles for DNA Delivery Applications.
复制标题
DOI：
10.1021/acs.biomac.0c01563
复制
发表时间：
2021-03-08
影响因子：
6.2
通讯作者：
Bryant SJ
中科院分区：
文献类型：
--
作者：
Anderson AJ;Grey E;Bongiardina NJ;Bowman CN;Bryant SJ
微粒介导的核酸传递是通过反义基因治疗实现治疗效果的一种流行策略。然而，目前用于制造聚合物微颗粒的方法存在诸如颗粒多分散性和低封装效率等不理想的性能。本文报道了一种基于阶梯生长巯基-迈克尔分散聚合的新型颗粒传递系统，该系统将低多分散性微粒与合成的核酸模拟物（即点击核酸（CNA））功能化。CNA低聚物的平均长度为腺嘌呤和胸腺嘧啶碱基的每条链大约有四个核酸重复单元，成功地与微粒中存在的过量硫醇偶联。通过简单的混合获得有效的DNA负载；并且，根据所用DNA的长度，最多可达到6±2 pmol /mg颗粒的互补DNA。此外，对于非互补序列和含有交替碱基错配的序列，DNA负载要少几个数量级。对DNA释放特性进行了评估，发现释放可以由温度的突然变化触发，但在ph范围内不受影响。最后，通过共聚焦显微镜观察到负载微颗粒的吞噬作用，并通过细胞代谢活性增加高达90%来证实。总的来说，这项工作表明，CNA功能化微粒可能是一个很有前途的平台，用于控制DNA传递。
Microparticle-mediated nucleic acid delivery is a popular strategy to achieve therapeutic outcomes via antisense gene therapy. However, current methods used to fabricate polymeric microparticles suffer from suboptimal properties such as particle polydispersity and low encapsulation efficiency. Here, a new particulate delivery system based on step-growth thiol-Michael dispersion polymerization, is reported in which a low polydispersity microparticle is functionalized with a synthetic nucleic acid mimic, namely click nucleic acids (CNA). CNA oligomers, exhibiting an average length of approximately four nucleic acid repeat units per chain for both adenine and thymine bases, were successfully conjugated to excess thiols present in the microparticles. Effective DNA loading was obtained by simple mixing; and, up to 6 ± 2 pmol of complementary DNA/mg of particle was achieved, depending on the length of DNA used. In addition, DNA loading was orders of magnitude less for noncomplementary sequences and sequences containing an alternating base mismatch. The DNA release properties were evaluated, and it was found that release could be triggered by sudden changes in temperature but was unaffected over a range of pH. Finally, phagocytosis of loaded microparticles was observed by confocal microscopy and corroborated by an increase in cellular metabolic activity up to 90%. Overall, this work suggests that CNA functionalized microparticles could be a promising platform for controlled DNA delivery.
登录
查看更多内容
影响因子：
3.7
作者：
Ferreiro, MG;Tillman, LG;Bodmeier, R
通讯作者：
Bodmeier, R
影响因子：
5.8
作者：
Bragagni, Marco;Esther Gil-Alegre, Maria;Mannelli, Lorenzo Di Cesare
通讯作者：
Mannelli, Lorenzo Di Cesare
影响因子：
14
作者：
Kasturi, SP;Sachaphibulkij, K;Roy, K
通讯作者：
Roy, K
DOI：
10.1016/j.ejpb.2008.09.007
发表时间：
2009-02-01
影响因子：
4.9
作者：
Ahmed, Abid Riaz;Bodmeier, Roland
通讯作者：
Bodmeier, Roland
影响因子：
10.8
作者：
Jiang S;Eltoukhy AA;Love KT;Langer R;Anderson DG
通讯作者：
Anderson DG