The optimal drug delivery system should be biocompatible, biodegradable, and allow the sustained release of the drug only after it reaches the target cells. Silk, as a natural polymer, is a great candidate for building drug carriers. Genetically engineered silks offer the possibility of functionalization. Previously, we characterized bioengineered silk spheres that were functionalized with H2.1 peptide that selectively delivered a drug to Her2-positive cancer cells. However, drug leakage from the silk spheres showed the need for improved control. To control the drug loading and release, we designed and produced functional silk (DOXMS2) that contains a DOX peptide with an affinity for doxorubicin. The DOXMS2 spheres showed the decreased release of doxorubicin compared with MS2 particles. Next, the DOXMS2 silk was blended with the H2.1MS1 polymer to improve the control of doxorubicin binding and release into Her2-positive cancer cells. The H2.1MS1:DOXMS2 particles showed the highest doxorubicin-loading capacity and binding per cell, which resulted in the highest cytotoxic effect compared with that of other sphere variants. Since drug release at a pH of 7.4 from the blended H2.1MS1:DOXMS2 particles was significantly lower than from blended spheres without DOXMS2 silk, this indicated that such particles could control the release of the drug into the circulatory system before the carrier reached the tumor site. This strategy, which is based on the blending of silks, allows for the generation of particles that deliver drugs in a controlled manner.

中文翻译：

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药物亲和力和靶向递送：丝球的双重功能化可将阿霉素受控递送至 Her2 阳性癌细胞中


最佳的药物递送系统应该具有生物相容性、可生物降解性，并且只有在药物到达靶细胞后才能持续释放。丝绸作为一种天然聚合物，是构建药物载体的绝佳候选者。基因工程丝绸提供了功能化的可能性。此前，我们对生物工程丝球进行了表征，该丝球被 H2.1 肽功能化，可选择性地将药物递送至 Her2 阳性癌细胞。然而，药物从丝球中泄漏表明需要改进控制。为了控制药物的装载和释放，我们设计并生产了功能性丝 (DOXMS2)，其中含有对阿霉素具有亲和力的 DOX 肽。与 MS2 颗粒相比，DOXMS2 球体显示阿霉素的释放减少。接下来，将 DOXMS2 丝与 H2.1MS1 聚合物混合，以改善对阿霉素结合和释放到 Her2 阳性癌细胞中的控制。 H2.1MS1:DOXMS2 颗粒显示出最高的阿霉素负载能力和每个细胞的结合力，与其他球体变体相比，这导致最高的细胞毒性作用。由于在 pH 7.4 时，混合 H2.1MS1:DOXMS2 颗粒的药物释放显着低于不含 DOXMS2 丝的混合球体，这表明此类颗粒可以在载体到达肿瘤之前控制药物释放到循环系统中地点。这种基于丝绸混合的策略可以产生以受控方式输送药物的颗粒。