Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Affiliated Hospital, Sun Yat-sen University, Guangdong 510080, People’s Republic of China.
Nanotechnology. 2013 Jul 5;24(26):265104. doi: 10.1088/0957-4484/24/26/265104.
To solve problems in polymersome preparation caused by liposolubility of copolymers and to improve the cytosolic delivery efficiency of polymersomes to drugs, a lipopolysaccharide-amine (LPSA) copolymer with amphotericity and amphiphilicity is developed. LPSA contains two hydrophilic oppositely charged blocks (anionic oxidized alginate (OA), cationic polyethyleneimine (PEI 1.8 k)) and one hydrophobic block (cholesteryl), where OA is the backbone and cholesteryl-grafted PEI is the side chain. The two hydrophilic blocks first guarantee that LPSA will dissolve in water, and then help polymersome formation via electrostatic interactions to generate water insoluble interpolyelectrolyte complexes, which supplement the hydrophobic part to reach the right hydrophilicity/hydrophobicity ratio, and thus realize a one-step self-assembly of polymersomes in water. Our results show LPSA nanopolymersomes (LNPs) have low cytotoxicity and degradability, and an excellent ability to enter cells. TEM observation demonstrates that LNPs are entrapped in endosomes after endocytosis, and are then released to cytosols because of their strong endosomal escape capacity. As an example of cytosolic delivery to bioactive molecules, pDNA is delivered in mesenchymal stem cells, and more than 95% of cells express a large target protein, indicating that LNPs have high cytosolic delivery efficiency. Our study provides a novel, easy, and universal method to design copolymers for the preparation of polymersomes as efficient cytosolic delivery nanocarriers.
为了解决共聚物脂溶性导致聚合物囊泡制备问题，并提高聚合物囊泡对药物的胞质内递送效率，开发了一种具有两性和两亲性的脂多糖-胺（LPSA）共聚物。LPSA 包含两个亲水性带相反电荷的链段（阴离子化氧化海藻酸钠（OA）、阳离子聚乙烯亚胺（PEI1.8k））和一个疏水性链段（胆固醇），其中 OA 是主链，胆固醇接枝的 PEI 是侧链。两个亲水性链段首先保证 LPSA 将溶解在水中，然后通过静电相互作用帮助聚合物囊泡形成，生成不溶于水的聚电解质复合物，补充疏水区以达到合适的亲水性/疏水性比例，从而在水中实现聚合物囊泡的一步自组装。我们的结果表明，LPSA 纳米聚合物囊泡（LNPs）具有低细胞毒性和可降解性，以及出色的细胞内进入能力。TEM 观察表明，LNPs 在细胞内吞作用后被内体包埋，然后由于其强大的内体逃逸能力而被释放到细胞质中。作为胞质内生物活性分子递送的一个例子，pDNA 在间充质干细胞中递送，超过 95%的细胞表达大量靶蛋白，表明 LNPs 具有很高的胞质内递送效率。我们的研究为设计用于制备聚合物囊泡作为高效胞质内递送纳米载体的共聚物提供了一种新的、简单的、通用的方法。
