Exogenous sources of amino acids are essential nutrients to fuel cancer growth. Here, the increased demand for amino acid displayed by cancer cells is unconventionally exploited as a design principle to replete cancer cells with apoptosis inducing nanoscopic porous amino acid mimics (Nano‐PAAM). A small library consisting of nine essential amino acids nanoconjugates (30 nm) are synthesized, and the in vitro anticancer activity is evaluated. Among the Nano‐PAAMs, l‐phenylalanine functionalized Nano‐PAAM (Nano‐pPAAM) has emerged as a novel nanotherapeutics with excellent intrinsic anticancer and cancer‐selective properties. The therapeutic efficacy of Nano‐pPAAM against a panel of human breast, gastric, and skin cancer cells could be ascribed to the specific targeting of the overexpressed human large neutral amino acid transporter SLC7A5 (LAT‐1) in cancer cells, and its intracellular reactive oxygen species (ROS) inducing properties of the nanoporous core. At the mechanistic level, it is revealed that Nano‐pPAAM could activate both the extrinsic and intrinsic apoptosis pathways to exert a potent “double‐whammy” anticancer effect. The potential clinical utility of Nano‐pPAAM is further investigated using an MDA‐MB‐231 xenograft in NOD scid gamma mice, where an overall suppression of tumor growth by 60% is achieved without the aid of any drugs or application of external stimuli.

中文翻译：

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设计有力：具有内在抗癌靶向特性的模仿多孔纳米疗法的氨基酸。

氨基酸的外源来源是促进癌症生长的重要营养素。在这里，非常规地利用癌细胞对氨基酸的需求增加作为一种设计原理，以利用凋亡诱导纳米级多孔氨基酸模拟物（Nano-PAAM）来补充癌细胞。合成了一个由九种必需氨基酸纳米缀合物（30 nm）组成的小文库，并评估了其体外抗癌活性。在Nano-PAAM中，l苯丙氨酸官能化的纳米PAAM（Nano-pPAAM）已经成为一种具有优异的内在抗癌和癌症选择性特性的新型纳米疗法。Nano-pPAAM对一组人乳腺癌，胃癌和皮肤癌细胞的治疗功效可归因于癌细胞中过表达的人类大型中性氨基酸转运蛋白SLC7A5（LAT-1）的特异性靶向及其细胞内反应性氧（ROS）诱导纳米多孔核的特性。从机理上看，Nano-pPAAM可以激活外在和内在的凋亡途径，从而发挥强大的“双重打击”抗癌作用。使用MDA‐MB‐231异种移植物对NOD scidγ小鼠进行了Nano-pPAAM潜在临床实用性的进一步研究，