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首页> 外文期刊>Journal of Materials Chemistry, B. materials for biology and medicine >pH-Responsive unimolecular micelles based on amphiphilic star-like copolymers with high drug loading for effective drug delivery and cellular imaging
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pH-Responsive unimolecular micelles based on amphiphilic star-like copolymers with high drug loading for effective drug delivery and cellular imaging

机译：基于高药物载荷和细胞成像的高药物载荷，基于两亲的星状共聚物的PH-响应浓度的单分子胶束

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Herein, we report pH-responsive star-like polymers (denoted as CPO) with amphiphilic diblock copolymers poly(2-(diisopropylamino) ethylmethacrylate)-b-poly[(ethylene glycol) methyl ether methacrylate] (PDPA-b-POEGMA) grafted from beta-cyclodextrin (beta-CD) for efficient antitumor drug delivery. A series of amphiphilic CPO polymers were synthesized via two-step atom transfer radical polymerization (ATRP) utilizing beta-CD-21Br as an initiator. Transmission electron microscopy and dynamic light scattering results demonstrated that these amphiphilic star-like polymers formed unimolecular micelles (UMs) in aqueous media and showed favorable robust micellar stability. The PDPA blocks are hydrophobic at pH = 7.4, which enabled these UMs to carry hydrophobic drugs such as doxorubicin (DOX) in their inner layer with a high drug loading content. Under an acidic environment, the hydrophobility-hydrophilicity transition of PDPA blocks induced the rapid pH-triggered release of drugs for cancer therapy. To endow these UMs with diagnostic functions, near-infrared fluorescent dye cyanine 5 (Cy5) was incorporated by post-decoration on the amine-functionalized precursor where their inner layer was replaced with copolymerized blocks of P(DPA-co-AMA). The UMs of the obtained Cy5 containing polymers (denoted as CPO-Cy5) exhibited switchable fluorescence in response to different pH conditions, where the fluorescence intensity could be enhanced by 7-fold with the change of pH from 9 to 4. The cytotoxicity experiments demonstrated that the DOX-loaded CPO or CPO-Cy5 micelles presented high cytotoxicity against HeLa and MCF-7 cancer cells but low cytotoxicity against normal L929 cells, likely implying their potential tumor-specific targeting ability. The integration of NIR imaging and effective therapeutic functions made DOX-loaded CPO-Cy5 a promising nanomedicine, providing new insights into the design of theranostic nanoplatforms.
机译：在此，我们向两亲二嵌段共聚物（2-（二异丙基）乙基丙烯酸甲酯）-b-poly [（乙二醇）甲基醚甲基丙烯酸酯（pdpa-b-poegma）接枝从β-环糊精（Beta-CD）用于有效的抗肿瘤药物递送。通过使用β-CD-21BR作为引发剂，通过两步原子转移自由基聚合（ATRP）合成一系列两亲硅CPO聚合物。透射电子显微镜和动态光散射结果表明，这些两亲的星状聚合物在含水介质中形成了单模胶束（UMS），并显示出有利的稳健胶束稳定性。 PDPA嵌段是pH = 7.4的疏水性，其使这些UM能够在其内层中携带疏水药，例如具有高药物负载含量的内层。在酸性环境下，PDPA嵌段的疏水性 - 亲水性转变诱导癌症治疗的快速pH-触发的药物。为了赋予诊断功能的这些UM，通过在胺官能化前体上的后装饰替代其内层的P（DPA-CO-AMA）替换它们的内层的近红外荧光染料花青5（CY5）。获得的Cy5的UMS含有聚合物（表示为CPO-CY5），响应于不同的pH条件表现出可切换的荧光，其中荧光强度可以通过7倍的pH从9-4的变化提高7倍。表明细胞毒性实验DOX加载的CPO或CPO-CY5胶束呈现出对HELA和MCF-7癌细胞的高细胞毒性，但对正常L929细胞的细胞毒性低，可能意味着它们潜在的肿瘤特异性靶向能力。 NIR成像和有效治疗功能的整合使DOX加载的CPO-CY5成为有前途的纳米医疗，为Theranostic Nanoplatforms的设计提供了新的见解。

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  • 作者

    Shi Xiaoxiao; Ma Xiaoqian; Hou Meili; Gao Yong-E; Bai Shuang; Xiao Bo; Xue Peng; Kang Yuejun; Xu Zhigang; Li Chang Ming;

  • 作者单位

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

    Southwest Univ Fac Mat &

    Energy Inst Clean Energy &

    Adv Mat Chongqing 400715 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分析化学;
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