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Synthesis of a phenylboronic ester-linked PEG-lipid conjugate for ROS-responsive drug delivery
Polymer Chemistry ( IF 4.1 ) Pub Date : 2017-08-04 00:00:00 , DOI: 10.1039/c7py00915a
Tianhui Zhang 1, 2, 3, 4, 5 , Xin Chen 1, 2, 3, 4, 5 , Chunsheng Xiao 1, 2, 3, 4, 5 , Xiuli Zhuang 1, 2, 3, 4, 5 , Xuesi Chen 1, 2, 3, 4, 5
Affiliation  

Stimuli-responsive drug delivery systems (DDSs) offering spatial-temporal and dosage controlled transport of drugs in vivo have attracted much attention for anticancer drug delivery. In the present work, a kind of phenylboronic ester-linked PEG-lipid conjugate was designed and synthesized for H2O2-responsive drug delivery. Firstly, a chain-end alkynyl functionalized methoxy poly(ethylene glycol) with a phenylboronic pinacol ester linker was synthesized via a classical Passerini reaction of carboxyl functionalized methoxy poly(ethylene glycol)2000 (mPEG2k-COOH), 4-formylphenylboronic pinacol ester and propargyl isocyanoacetamide. The obtained polymer was denoted as mPEG2k-PBPE-alkynyl. Then, the oxidation-responsive cleavage of the phenylboronic pinacol ester linker between the mPEG2k-COOH and alkynyl chain-end was verified by in situ1H NMR and mass spectra characterization. Furthermore, the amphiphilic PEG-lipid conjugate was synthesized by the Cu(I)-catalyzed click reaction of mPEG2k-PBPE-alkynyl and 3-azido-1,2-propanediol distearate (N3-DSA). The resultant mPEG2k-PBPE-DSA could self-assemble into stable micelles in aqueous media. Nile red was used as the model drug and was loaded into the micelles. The obtained drug loaded micelles exhibited a typical H2O2-responsive drug release behavior and could be effectively internalized by MCF-7 cells. In addition, the synthesized mPEG2k-PBPE-DSA was tested to be nontoxic towards RAW264.7 cells. Therefore, this biocompatible mPEG2k-PBPE-DSA conjugate would be promising for applications in ROS-responsive drug delivery.

中文翻译:

苯硼酸酯连接的PEG-脂质共轭物的合成,用于ROS响应药物的递送

提供体内时空和剂量控制的体内药物传递的刺激响应药物传递系统(DDS)抗癌药物传递方面引起了广泛关注。在目前的工作中,设计并合成了一种苯基硼酸酯连接的PEG-脂质共轭物,用于H 2 O 2响应药物递送。首先,通过羧基官能化的甲氧基聚(乙二醇)2000(mPEG 2k -COOH),4-甲酰基苯基硼酸频哪醇酯和炔丙基异氰基乙酰胺。所得聚合物表示为mPEG。2k -PBPE-炔基。然后,通过原位1 H NMR和质谱表征验证了mPEG 2k -COOH和炔基链端之间的苯基硼酸频哪醇酯连接基的氧化反应性裂解。此外,通过Cu( I)催化的mPEG 2k -PBPE-炔基和3-叠氮基-1,2-丙二醇二硬脂酸酯(N 3 -DSA)的点击反应合成了两亲性PEG-脂质缀合物。所得的mPEG 2k -PBPE-DSA可以在水性介质中自组装成稳定的胶束。尼罗河红被用作模型药物,并被装入胶束中。获得的载药胶束表现出典型的H 2 O 2。反应性药物释放行为,可以被MCF-7细胞有效地内化。此外,测试了合成的mPEG 2k -PBPE-DSA对RAW264.7细胞无毒。因此,这种具有生物相容性的mPEG 2k -PBPE-DSA共轭物有望在ROS反应性药物递送中得到应用。
更新日期:2017-10-17
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