pH-responsive diblock copolymers provide tailorable nanoparticle (NP) architecture and chemistry critical for siRNA delivery. Here, diblock polymers varying in first (corona) and second (core) block molecular weight (M_n), corona/core ratio, and core hydrophobicity (%BMA) were synthesized to determine their effect on siRNA delivery in murine tenocytes (mTenocyte) and murine and human mesenchymal stem cells (mMSC and hMSCs, respectively). NP-mediated siRNA uptake, gene silencing, and cytocompatibility were quantified. Uptake is positively correlated with first block M_n in mTenocytes and hMSCs (p ≤ 0.0005). All NP resulted in significant gene silencing that was positively correlated with %BMA (p < 0.05) in all cell types. Cytocompatibility was reduced in mTenocytes compared to MSCs (p < 0.0001). %BMA was positively correlated with cytocompatibility in MSCs (p < 0.05), suggesting stable NP are more cytocompatible. Overall, this study shows that NP-siRNA cytocompatibility is cell type dependent, and hydrophobicity (%BMA) is the critical diblock copolymer property for efficient gene silencing in musculoskeletal cell types.

中文翻译：

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Diblock共聚物疏水性促进高效基因沉默和细胞相容性纳米粒子介导的siRNA传递到骨骼肌细胞类型。

pH响应性二嵌段共聚物可提供可定制的纳米颗粒（NP）结构和化学性质，这对siRNA的传递至关重要。在这里，合成了在第一（电晕）和第二（核心）嵌段分子量（M _n），电晕/核心比率和核心疏水性（％BMA）不同的二嵌段聚合物，以确定它们对鼠肌腱细胞（mTenocyte）中siRNA递送的影响。以及鼠和人间充质干细胞（分别为mMSC和hMSC）。NP介导的siRNA摄取，基因沉默和细胞相容性进行了量化。摄取是积极与第一块相关中号_Ñ在mTenocytes和的hMSC（p ≤0.0005）。所有NP导致显着的基因沉默与％BMA正相关（p<0.05）。与MSC相比，mTenocytes的细胞相容性降低（p <0.0001）。％BMA与MSC中的细胞相容性呈正相关（p <0.05），表明稳定的NP具有更好的细胞相容性。总体而言，这项研究表明NP-siRNA的细胞相容性取决于细胞类型，而疏水性（％BMA）是在肌肉骨骼细胞类型中有效沉默基因的关键二嵌段共聚物特性。