Peptides have shown great potential in acting as template for developing versatile carrier platforms in nanomedicine, aimed at selective delivery of drugs to only pathological tissues saving its normal neighbors. Cell‐penetrating peptides (CPPs) are short oligomeric peptides capable of translocating across the cell membrane while simultaneously employing multiple mechanisms of entry. Most CPPs exist as disordered structures in solution and may adopt a helical conformation on interaction with cell membrane, vital to their penetrative capability. Herein, we report a series of cationic helical amphipathic peptides (CHAPs), which are topologically constrained to be helical. The peptides were tested against cervical and breast cancer cells for their cell penetration and drug delivery potential. The cellular uptake of CHAP peptides is independent of temperature and energy availability. The activity of the peptides is biocompatible in bovine serum. CHAPs delivered functional methotrexate (MTX) inside the cell as CHAP‐MTX conjugates. CHAP‐MTX conjugates were more toxic to cancer cells than MTX alone. However, the CHAP‐MTX conjugates were less toxic to HEK‐293 cells compared with the cancer cells suggesting higher affinity towards cancer cells.

中文翻译：

---

用于药物递送的构象受限的肽。

肽已显示出巨大潜力，可作为开发纳米医学多功能载体平台的模板，旨在将药物选择性地仅递送至病理组织，从而拯救其正常邻居。细胞穿透肽（CPP）是短的寡聚肽，能够跨细胞膜转运，同时采用多种进入机制。大多数CPP在溶液中以无序结构形式存在，并且在与细胞膜相互作用时可能会采用螺旋构象，这对它们的穿透能力至关重要。在本文中，我们报告了一系列阳离子螺旋两亲性肽（CHAP），它们在拓扑上被约束为螺旋形。测试了针对宫颈和乳腺癌细胞的肽的细胞渗透性和药物递送潜力。CHAP肽的细胞摄取与温度和能量可用性无关。肽的活性在牛血清中具有生物相容性。CHAP以CHAP-MTX偶联物的形式在细胞内递送功能性甲氨蝶呤（MTX）。CHAP-MTX缀合物对癌细胞的毒性比单独的MTX高。但是，与癌细胞相比，CHAP-MTX共轭物对HEK-293细胞的毒性较小，表明对癌细胞的亲和力更高。