Abstract We report a class of 17-amino-acid peptides that undergo a sharp hydrophobicity transition at pH around 7. Nanoparticles made of such peptides exhibit ultra pH-sensitivity and autonomous drug-eluting properties, which are beneficial for cancer drug delivery. At pH above 7, the peptides bind water-insoluble drug cargo and form a nanoparticle that protects its cargo from serum proteins. Sensing tumor's mildly acidic pH (≤7.0), nanoparticle peptides undergo a hydrophobic-to-hydrophilic transition and release drug molecules in the interstitial fluid as the nanoparticle migrates down the pH gradient in the tumor. When this pH-sensing and drug-eluting nanoparticle formulation was used to deliver two drugs, lonidamine inhibiting tumor bioenergetics and bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) targeting cancer glutamine metabolism, to triple negative human breast cancer xenografts, the nanoparticle drug demonstrated superior efficiency compared to the respective standard formulation.

中文翻译：

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具有pH感应货物溶解度的肽纳米颗粒可提高抗癌药物效率

摘要 我们报告了一类 17 个氨基酸的肽，它们在 pH 值约为 7 时经历了急剧的疏水性转变。由这些肽制成的纳米颗粒表现出超 pH 敏感性和自主药物洗脱特性，有利于癌症药物的递送。在 pH 值高于 7 时，肽与水不溶性药物货物结合并形成纳米颗粒，保护其货物免受血清蛋白的影响。感知肿瘤的弱酸性 pH (≤7.0)，纳米颗粒肽经历疏水到亲水的转变，并在纳米颗粒沿肿瘤中的 pH 梯度向下迁移时在间质液中释放药物分子。当这种 pH 感应和药物洗脱纳米颗粒制剂用于递送两种药物时，氯尼达明抑制肿瘤生物能量学和双 2-(5-苯基乙酰氨基-1,2,