Self-assembled nanoparticles from thiol functionalized liquid crystalline brush block copolymers for dual encapsulation of doxorubicin and gold nanoparticles
Self-assembled nanoparticles from thiol functionalized liquid crystalline brush block copolymers for dual encapsulation of doxorubicin and gold nanoparticles
复制标题
DOI：
10.1039/c3py01636f
复制
发表时间：
2014-01-01
影响因子：
4.6
通讯作者：
Kasi, Rajeswari M.
中科院分区：
文献类型：
--
作者：
Chi Thanh Nguyen;Thanh Huyen Tran;Kasi, Rajeswari M.
我们合成了新的两亲性刷状液晶嵌段共聚物（brush-chol-BCP）的聚甲基丙烯酸酯轴承聚环氧乙烷（PEO）在一个嵌段和聚甲基丙烯酸酯轴承胆固醇介晶与半遥爪硫醇端基。采用可逆加成-断裂链转移聚合（RAFT）法合成了聚甲基丙烯酸酯（PMA-g-PEO），并以其为大分子链转移剂合成了嵌段共聚物（PMA-g-PEO）-b-PC_5 MA-硫酯（brush-chol-BCP-硫酯）。刷-胆-BCP-硫醇通过在丁胺存在下将硫酯还原成硫醇来获得。通过还原金离子，用刷状-chol-BCP-硫醇模板原位制备金纳米颗粒（AuNPs），并通过与共聚物中的硫醇基团的配位键直接锚定到刷状-chol-BCP-硫醇链上来稳定金纳米颗粒。将疏水性抗癌药物阿霉素（DOX）通过物理包封成功地包封到以金纳米粒子为模板的刷状胆固醇-BCP-硫醇中，形成具有21.4%（w/w）的高载药量和85.6%的高包封率的双包封纳米粒子。双包封纳米粒的平均粒径为157 nm，球形，具有良好的稳定性和持续的药物释放模式。更重要的是，双包封的纳米颗粒可以有效地被人宫颈癌细胞（Hela）内化，并显示出剂量依赖性的细胞毒性，而空白纳米颗粒在测试浓度下无细胞毒性。结果表明刷-胆-BCP-硫醇及其纳米颗粒是用于抗癌药物和金属纳米颗粒的双重包封和递送的有前途的载体。
We synthesized new amphiphilic brush liquid crystalline block copolymers (brush-chol-BCP) comprised of polymethacrylates bearing polyethylene oxide (PEO) in one block and polymethacrylates bearing a cholesterol mesogen with a hemitelechelic thiol end group. Polymethacrylate bearing PEO (PMA-g-PEO) was first synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) and used as a macro-chain transfer agent to prepare block copolymer (PMA-g-PEO)-b-PC5MA-thioester (brush-chol- BCP-thioester). Brush-chol-BCP-thiol was obtained by the reduction of a thioester to thiol in the presence of butylamine. Gold nanoparticles (AuNPs) were prepared in situ with the brush-chol-BCP-thiol template via the reduction of gold ions and were stabilized by directly anchoring to the brush-chol-BCP-thiol chains through the coordination bonds with the thiol groups in the copolymer. The hydrophobic anticancer drug doxorubicin (DOX) was successfully encapsulated into AuNP-templated brush-chol-BCP-thiol via physical entrapment to form dual-encapsulated NPs with a high drug loading of 21.4% (w/w) and a high encapsulation efficiency of 85.6%. The dual-encapsulated NPs had an average size of 157 nm, spherical shape, excellent stability, and a sustained drug release pattern. More importantly, the dual-encapsulated NPs could be effectively internalized by human cervical cancer cells (Hela) and showed dose-dependent cytotoxicity, while the blank nanoparticles were non-cytotoxic at the tested concentrations. The results indicate that the brush-chol-BCP-thiol and their nanoparticles are promising carriers for dual encapsulation and delivery of an anticancer drug and metal nanoparticles.