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首页> 外文期刊>Bioconjugate Chemistry >Amphiphilic Glycopolypeptide Star Copolymer-Based Cross-Linked Nanocarriers for Targeted and Dual-Stimuli-Responsive Drug Delivery
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Amphiphilic Glycopolypeptide Star Copolymer-Based Cross-Linked Nanocarriers for Targeted and Dual-Stimuli-Responsive Drug Delivery

机译：含有靶向和双刺激响应药物递送的两亲型甘油肽基族共聚物的交联纳米载体

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摘要

Glycopolypeptide-based nanocarriers are an attractive class of drug delivery vehicles because of the involvement of carbohydrates in the receptor-mediated endocytosis process. To enhance their efficacy toward controlled and programmable drug delivery, we have prepared stable glycopolypeptide-based bioactive dual-stimuli-responsive (redox and enzyme) micelles for delivery of anticancer drugs specifically to the cancer cells. The amphiphilic biocompatible miktoarm star copolymer, which comprises two hydrophobic poly(epsilon-caprolactone) blocks, a short poly-(propargyl glycine) middle block, and a hydrophilic galactose glycopolypeptide block, was designed and synthesized. The star copolymer is initially self-assembled into un-cross-linked (UCL) micelles, and free alkyne groups at the core shell interface of the UCL micelles, which were cross-linked by bis(azidoethyl) disulfide (BADS) via click chemistry to form interface cross linked (ICL) micelles. ICL micelles were found to be stable against dilution. BADS imparted redox-responsive properties to the micelles, while PCL rendered them enzyme-degradable. Dual-stimuli-responsive release behavior with Dox as model drug was studied individually as well as synergistically by applying two stimuli in different sequences. The galactose-containing UCL and ICL micelles were shown to be nontoxic. Intracellular Dox release from UCL and ICL micelles was demonstrated in liver cancer cells (HepG2) by time-dependent cellular uptake studies, and controlled release from ICL micelles compared to UCL micelles was observed. The present report opens a new approach toward targeted and programmable drug delivery in tumor tissues via a specifically targeted (receptor-mediated), dual-responsive, and stable cross-linked nanocarrier system.
机译：基于甘草基肽的纳米载体是一种吸引人的药物递送载体，因为碳水化合物在受体介导的内吞作用过程中的累积。为了增强它们对受控和可编程药物递送的功效，我们制备了稳定的基于甘草肽的生物活性双刺激响应（氧化还原和酶）胶束，用于特异性地向癌细胞递送抗癌药物。构成和合成包含两个疏水聚（ε-己内酯）嵌段，短聚（炔丙基甘氨酸）中间嵌段和亲水半乳糖甘露出酶嵌段的两亲性生物相容性MikoArm星共聚物。首先将恒星共聚物自组装成未交联的（UCL）胶束，并在UCL胶束的核心壳界面处的游离炔基，通过双（偶氮乙基）二硫化物（坏）通过点击化学交联形成接口交叉链接（ICL）胶束。发现ICL胶束稳定稀释。不良赋予胶束氧化还原响应性，而PCL使其酶降解。通过在不同序列中施加两种刺激，单独研究与DOX作为模型药物的双刺激循环行为。显示半乳糖的UCL和ICL胶束被显示为无毒。通过时间依赖的蜂窝摄取研究在肝癌细胞（HepG2）中对UCL和ICL胶束的细胞内DOX释放，并观察到与UCL胶束相比的ICL胶束的控制释放。本报告通过特异性靶向（受体介导），双响应和稳定的交联纳米载体系统为肿瘤组织中针对靶向和可编程药物递送的新方法。

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  • 来源
    《Bioconjugate Chemistry》 |2019年第3期|共14页
  • 作者

    Pandey Bhawana; Patil Naganath G.; Bhosle Govind S.; Arnbade Ashootosh V.; Sen Gupta Sayam;

  • 作者单位

    CSIR Natl Chem Lab Polymer Sci &

    Engn Div Dr Homi Bhabha Rd Pune 411008 Maharashtra India;

    CSIR Natl Chem Lab Polymer Sci &

    Engn Div Dr Homi Bhabha Rd Pune 411008 Maharashtra India;

    CSIR Natl Chem Lab Organ Chem Div Dr Homi Bhabha Rd Pune 411008 Maharashtra India;

    CSIR Natl Chem Lab Polymer Sci &

    Engn Div Dr Homi Bhabha Rd Pune 411008 Maharashtra India;

    Indian Inst Sci Educ &

    Res Dept Chem Sci Kolkata 741246 India;

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  • 正文语种 eng
  • 中图分类 生物化学;
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  • 入库时间 2022-08-19 23:05:32

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