Synthesis of ABA Tri-Block Co-Polymer Magnetopolymersomes via Electroporation for Potential Medical Application
Synthesis of ABA Tri-Block Co-Polymer Magnetopolymersomes via Electroporation for Potential Medical Application
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DOI：
10.3390/polym7121529
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发表时间：
2015-12
期刊：
影响因子：
5
通讯作者：
Jennifer Bain;Matthew E Berry;Catherine E. Dirks;Sarah S. Staniland
中科院分区：
文献类型：
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作者：
Jennifer Bain;Matthew E Berry;Catherine E. Dirks;Sarah S. Staniland
已知阿坝三嵌段共聚物聚（2-甲基恶唑啉）-聚（二甲基硅氧烷）-聚（2-甲基恶唑啉）（PMOXA-PDMS-PMOXA）具有模拟双层膜的能力，因为它能够形成囊泡聚合物囊泡结构。出于这个原因，它是广泛研究的主题，并能够开发用于生物医学应用的天然脂质体的更强大，适应性和生物相容性的替代品。然而，这种聚合物的溶解性差使得公开的用于形成囊泡的方法不可再现，阻碍了这些聚合物囊泡的研究和开发。在这里，我们提出了一种适用的，更简单的方法，用于生产PMOXA-PDMS-PMOXA聚合物囊泡的窄多分散性（45 ± 5.8 nm），通过缓慢加入水溶液到一个新的溶剂/聚合物混合物。然后，我们磁性官能化这些聚合物囊泡，形成磁性聚合物囊泡通过原位沉淀的氧化铁磁性纳米粒子（MNP）内的PMOXA-PDMS-PMOXA聚合物囊泡核心和膜。这是使用电穿孔来打开膜内的孔并激活MNP的形成来实现的。众所周知，厚PMOXA-PDMS-PMOXA膜与更常用的二嵌段聚合物膜相比是相对不可渗透的，这是由于尺寸和化学性质的明显差异，因此使用标准生物学方法很难渗透。本文首次介绍了电穿孔在阿坝三嵌段聚合物囊泡膜（PMOXA-PDMS-PMOXA）上的应用，用于囊泡内原位沉淀均匀的MNP（2.6 ± 0.5 nm）。电穿孔过程促进MNP反应物穿过膜的运输，产生MNP的原位沉淀。除了长度和化学性质的差异之外，三嵌段聚合物囊泡膜结构不同于天然脂质或二嵌段聚合物膜，因此电穿孔在这种类型的聚合物囊泡上的应用和效果是完全新颖的。一种机制被假设来解释这些生物医学上适用的三嵌段磁性聚合物的最终结构和组成。
The ABA tri-block copolymer poly(2-methyloxazoline)–poly(dimethylsiloxane)–poly(2-methyloxazoline) (PMOXA–PDMS–PMOXA) is known for its capacity to mimic a bilayer membrane in that it is able to form vesicular polymersome structures. For this reason, it is the subject of extensive research and enables the development of more robust, adaptable and biocompatible alternatives to natural liposomes for biomedical applications. However, the poor solubility of this polymer renders published methods for forming vesicles unreproducible, hindering research and development of these polymersomes. Here we present an adapted, simpler method for the production of PMOXA–PDMS–PMOXA polymersomes of a narrow polydispersity (45 ± 5.8 nm), via slow addition of aqueous solution to a new solvent/polymer mixture. We then magnetically functionalise these polymersomes to form magnetopolymersomes via in situ precipitation of iron-oxide magnetic nanoparticles (MNPs) within the PMOXA–PDMS–PMOXA polymersome core and membrane. This is achieved using electroporation to open pores within the membrane and to activate the formation of MNPs. The thick PMOXA–PDMS–PMOXA membrane is well known to be relatively non-permeable when compared to more commonly used di-block polymer membranes due a distinct difference in both size and chemistry and therefore very difficult to penetrate using standard biological methods. This paper presents for the first time the application of electroporation to an ABA tri-block polymersome membrane (PMOXA–PDMS–PMOXA) for intravesicular in situ precipitation of uniform MNPs (2.6 ± 0.5 nm). The electroporation process facilitates the transport of MNP reactants across the membrane yielding in situ precipitation of MNPs. Further to differences in length and chemistry, a tri-block polymersome membrane structure differs from a natural lipid or di-block polymer membrane and as such the application and effects of electroporation on this type of polymersome is entirely novel. A mechanism is hypothesised to explain the final structure and composition of these biomedically applicable tri-block magnetopolymersomes.