Abstract The controlled delivery of drugs towards the cancerous cell is still an unresolved issue in the area of cancer cell targeted drug delivery. To resolve the issue, in this work, a triple-responsive (pH, magnetic field and redox) nanogel has been fabricated to potentially deliver the anticancer drug (DOX) to the cancerous cell. The nanogel has been fabricated by esterification reaction between the ‘-COOH’ group of the pre-synthesized amphiphilic tetra-armed block copolymer, pentaerythritol-poly(e-caprolactone)-b-polyacrylic (Pe-PCL-b-PAA) and ‘-OH’ group of the redox-responsive crosslinker, 2-hydroxyethyl disulfide. The nanogels are further ornamented with aminosilane coated magnetic nanoparticles to impart the magnetic field responsive characteristic. The spherically shaped nanogel (size 120 nm) ensures the long circulation half-life in the bloodstream. The drug release profile under different stimuli such as pH, magnetic field and redox environment explored a new way of controlled drug release in a more promising manner under the synergistic participation of all three stimuli. It has been observed that the multi-stimuli responsive nanogel not only boost up the cell uptake process but also dramatically enhance the drug release rate up to 65% within 1 h under the environment of multiple stimuli (acidic pH 5, redox (10 mM GSH) and in the presence of dynamic magnetic field. Precisely, the acidic pH and reducing micro-environment of cancer affected cells are expected to act as an internal stimulus, whereas magnetic force can be maneuverer as an external stimulus in the proposed sub-structure of the nanogels. In a nut-shell, this kind of multi-responsive nanogel can pave a new direction in the area of controlled and targeted delivery of anticancer drugs or other biomolecules.

中文翻译：

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用于增强细胞内药物递送的磁性粒子锚定还原和 pH 响应纳米凝胶

摘要 靶向癌细胞的药物控制递送仍然是癌细胞靶向药物递送领域的一个悬而未决的问题。为了解决这个问题，在这项工作中，制造了一种三重响应（pH、磁场和氧化还原）纳米凝胶，以潜在地将抗癌药物 (DOX) 输送到癌细胞。纳米凝胶是通过预先合成的两亲性四臂嵌段共聚物季戊四醇-聚（e-己内酯）-b-聚丙烯酸（Pe-PCL-b-PAA）和'-COOH'基团之间的酯化反应制备的。 -OH' 基团的氧化还原响应交联剂，2-羟乙基二硫化物。纳米凝胶进一步装饰有氨基硅烷涂覆的磁性纳米粒子，以赋予磁场响应特性。球形纳米凝胶（尺寸 120 nm）确保在血流中具有较长的循环半衰期。pH、磁场和氧化还原环境等不同刺激下的药物释放曲线探索了一种在所有三种刺激的协同参与下以更有前途的方式控制药物释放的新途径。已经观察到，在多重刺激（酸性 pH 5，氧化还原（10 mM GSH）环境下，多刺激响应纳米凝胶不仅可以促进细胞摄取过程，而且可以在 1 小时内显着提高药物释放率高达 65% ) 并且在动态磁场的存在下。确切地说，受癌症影响的细胞的酸性 pH 值和还原微环境有望作为内部刺激，而在纳米凝胶的拟议子结构中，磁力可以作为外部刺激进行操纵。简而言之，这种多响应纳米凝胶可以为抗癌药物或其他生物分子的受控和靶向递送领域开辟新的方向。