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Inclusion of a pH‑responsive amino acid‑based amphiphile in methotrexate‑loaded chitosan nanoparticles as a delivery strategy in cancer therapy

机译:在甲氨蝶呤负载的壳聚糖纳米颗粒中加入基于pH值的基于氨基酸的两亲物,作为癌症治疗中的一种递送策略

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摘要

The encapsulation of antitumor drugs in nanosized systems with pH-sensitive behavior is a promising approach that may enhance the success of chemotherapy in many cancers. The nanocarrier dependence on pH might trigger an efficient delivery of the encapsulated drug both in the acidic extracellular environment of tumors and, especially, in the intracellular compartments through disruption of endosomal membrane. In this context, here we reported the preparation of chitosan-based nanoparticles encapsulating methotrexate as a model drug (MTX-CS-NPs), which comprises the incorporation of an amino acid-based amphiphile with pH-responsive properties (77KS) on the ionotropic complexation process. The presence of 77KS clearly gives a pH-sensitive behavior to NPs, which allowed accelerated release of MTX with decreasing pH as well as pH-dependent membrane-lytic activity. This latter performance demonstrates the potential of these NPs to facilitate cytosolic delivery of endocytosed materials. Outstandingly the cytotoxicity of MTX-loaded CS-NPs was higher than free drug to MCF-7 tumor cells and, to a lesser extent, to HeLa cells. Based on the overall results, MTX-CS-NPs modified with the pH-sensitive surfactant 77KS could be potentially useful as a carrier system for intracellular drug delivery and, thus, a promising targeting anticancer chemotherapeutic agent.
机译:在具有pH敏感行为的纳米系统中封装抗肿瘤药物是一种有前途的方法,可以增强许多癌症中化学疗法的成功率。纳米载体对pH的依赖性可能会在肿瘤的酸性细胞外环境中,尤其是通过破坏内体膜在细胞内区室中触发封装药物的有效递送。在这种情况下,我们报道了壳聚糖基纳米颗粒的制备,该纳米颗粒包封了甲氨蝶呤作为模型药物(MTX-CS-NPs),其中包括在离子性上掺入具有pH响应特性的氨基酸两亲物(77KS)络合过程。 77KS的存在清楚地赋予了NP一个pH敏感的行为,这使得MTX可以随着pH的降低以及依赖于pH的膜分解活性而加速释放。后一种性能证明了这些NP促进内吞材料的胞质递送的潜力。出乎意料的是,MTX负载的CS-NPs对MCF-7肿瘤细胞的毒性高于游离药物,对HeLa细胞的毒性较小。根据总体结果,用pH敏感表面活性剂77KS修饰的MTX-CS-NPs可能潜在地用作细胞内药物输送的载体系统,因此有望成为靶向的抗癌化学治疗剂。

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