基于肽的纳米材料可以作为有前途的药物递送剂,促进活性药物成分的释放,同时降低不良反应的风险。我们先前证明了环-组氨酸-组氨酸(Cyclo-HH),与癌症药物表柔比星共组装,锌,和硝酸根离子,可以构成一个有吸引力的药物递送系统,结合药物自封装,增强荧光,以及将药物运送到细胞中的能力。这里,我们通过计算和实验研究了Cyclo-HH是否可以共组装,在锌和硝酸根离子的存在下,与其他具有不同理化性质的抗癌药物。我们的研究表明甲氨蝶呤,除了表阿霉素及其差向异构体阿霉素,和较小程度的丝裂霉素-C和5-氟尿嘧啶,有能力与Cyclo-HH共同组装,锌,和硝酸根离子,而顺铂的倾向显着降低。表阿霉素,阿霉素,甲氨蝶呤显示出改善的药物包封和药物释放性能,与丝裂霉素C和5-氟尿嘧啶相比。我们展示了共组装系统的生物相容性,以及它们在细胞内释放药物的能力,特别是表阿霉素,阿霉素,还有甲氧蝶呤.锌和硝酸盐被证明在共同组装中很重要,与药物和/或Cyclo-HH协调,从而在成功形成的纳米载体中实现药物-肽以及药物-药物相互作用。这些见解可用于具有改进特性的先进癌症治疗系统的未来设计。
Peptide-based nanomaterials can serve as promising drug delivery agents, facilitating the release of active pharmaceutical ingredients while reducing the risk of adverse reactions. We previously demonstrated that Cyclo-Histidine-Histidine (Cyclo-HH), co-assembled with cancer drug Epirubicin, zinc, and nitrate ions, can constitute an attractive drug delivery system, combining drug self-encapsulation, enhanced fluorescence, and the ability to transport the drug into cells. Here, we investigated both computationally and experimentally whether Cyclo-HH could co-assemble, in the presence of zinc and nitrate ions, with other cancer drugs with different physicochemical properties. Our studies indicated that Methotrexate, in addition to Epirubicin and its epimer Doxorubicin, and to a lesser extent Mitomycin-C and 5-Fluorouracil, have the capacity to co-assemble with Cyclo-HH, zinc, and nitrate ions, while a significantly lower propensity was observed for Cisplatin. Epirubicin, Doxorubicin, and Methorexate showed improved drug encapsulation and drug release properties, compared to Mitomycin-C and 5-Fluorouracil. We demonstrated the biocompatibility of the co-assembled systems, as well as their ability to intracellularly release the drugs, particularly for Epirubicin, Doxorubicin, and Methorexate. Zinc and nitrate were shown to be important in the co-assembly, coordinating with drugs and/or Cyclo-HH, thereby enabling drug-peptide as well as drug-drug interactions in successfully formed nanocarriers. The insights could be used in the future design of advanced cancer therapeutic systems with improved properties.