调节含羧酸侧链的聚丙烯酸酯的细胞相互作用：花青染料标签和侧链类型的作用。,Biomacromolecules

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调节含羧酸侧链的聚丙烯酸酯的细胞相互作用：花青染料标签和侧链类型的作用。
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-06-29 , DOI: 10.1021/acs.biomac.0c00244
Ayaat M Mahmoud ₁ , Joshua P Morrow ₁ , David Pizzi ₁ , Ailsa M Azizah ₁ , Thomas P Davis _{1,

2} , Rico F Tabor ₃ , Kristian Kempe _{1,

4}

Affiliation

细胞吸收和细胞内靶向特定细胞器是纳米材料细胞加工中的关键事件。本文中，我们对含羧酸侧链的聚丙烯酸酯进行了详细的结构-性质关系研究，以提供操纵其细胞相互作用的设计标准。三种不同取代度和聚合度（DPs）的叔丁基保护的N-酰化氨基酯基丙烯酸酯单体的氧化还原引发的可逆加成-断裂链转移（RRAFT）聚合产生了确定的且pH响应的羧酸侧脱保护后的链状聚合物（N-乙酰基，DP 1：P（M ₁）；N-丙酰基，DP 1：P（E ₁），DP 2：P（E ₂））。流式细胞术研究显示时间依赖性细胞与P（E ₂）> P（E ₁）> P（M _1）相关）在任何给定的时间点。重要的是，发现用于标记的花青染料的类型显着影响聚合物的细胞加工。将染料从Cy5变为其磺化版本sulfoCy5导致细胞缔合力大大降低。此外，Cy5标记的聚合物靶向线粒体，而磺基Cy5修饰导致聚合物向溶酶体运输的细胞命运发生重大变化。这项研究突出了选择合适染料的重要性，但也证明了合理设计羧化聚丙烯酸酯的细胞器特异性靶向的可能性。

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Tuning Cellular Interactions of Carboxylic Acid-Side-Chain-Containing Polyacrylates: The Role of Cyanine Dye Label and Side-Chain Type.

Cellular uptake and intracellular targeting to specific organelles are key events in the cellular processing of nanomaterials. Herein, we perform a detailed structure–property relationship study on carboxylic acid-side-chain-bearing polyacrylates to provide design criteria for the manipulation of their cellular interactions. Redox-initiated reversible addition-fragmentation chain-transfer (RRAFT) polymerization of three tert-butyl-protected N-acylated amino ester-based acrylate monomers of different substitutions and degrees of polymerization (DPs) yielded defined and pH-responsive carboxylic acid-side-chain polymers upon deprotection (N-acetyl, DP 1: P(M₁); N-propionyl, DP 1: P(E₁), DP 2: P(E₂)). Flow cytometry studies revealed time-dependent cell association with P(E₂) > P(E₁) > P(M₁) at any given time point. Importantly, the type of cyanine dye used for labeling was found to significantly influence the cellular processing of the polymers. Changing the dye from Cy5 to its sulfonated version sulfoCy5 resulted in a much lower cellular association. Moreover, Cy5-labeled polymers were targeted to mitochondria, while sulfoCy5 modification caused a significant change in the cellular fate of polymers toward lysosome trafficking. This study highlights the importance of selecting a suitable dye but also demonstrates the possibilities for the rational design of organelle-specific targeting of carboxylated polyacrylates.

更新日期：2020-08-10

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