Four peptide amphiphiles (PA1-4) with different degrees of polymerization (DP = 40, 15, 10, and 6) were synthesized by Fuchs-Farthing and ring-opening polymerization followed by post-polymerization modification, as fully characterized by ¹H NMR, FT-IR, gel permeation chromatography, and circular dichroism (CD) spectroscopy. It was found that PAs could self-assemble to form regular spherical micelles in low-concentration (about 1 mg/mL) aqueous solution, which had different contents of secondary structures and mainly adopted random coil conformations. The water solubility of PAs increases with the increase of DP, the polypeptide chain stretches randomly in water, the β-sheets decrease, and the random coil conformations dominate. When the pH of PA solution decreases or increases, intramolecular hydrogen bonds break, and molecular chains stretch, leading to a decrease of α-helix, turn conformations, and an increase of β-sheets. Meanwhile, the particle size of micelles increases. At around 0.4 mg/mL, the hemolysis ability of PA2 is negligible at pH 7.4 and 6.5 and about 33% at pH 5.5. Cisplatin (CDDP) was linked to micelles by coordination bonds to explore their potential as drug carriers, exhibiting controlled pH and reduction in dual drug release effects. MTT assay showed that the HeLa cell viability was 78% when cultured in the 13.5 μg/mL PA2 blank micelles for 2 days, while the cell viability was 60% in the CDDP-loaded micelles. Furthermore, a high concentration of PA2 (about 100 mg/mL) could self-assemble into a fibrous hydrogel at pH 5.5, which self-healed 2 h after incision and self-degraded 71% within 14 days. The CDDP-loaded fiber hydrogel exhibited a sustained release effect similar to the CDDP-loaded micelles. The cytotoxicity of CDDP-loaded fibers at 48 h was detected to be the same as that of the same amount of CDDP, and the cell viability was 7%. Therefore, we provide a new strategy for the synthesis of amphiphilic peptides with potential applications in nano-drug carriers and cancer therapy.

中文翻译：

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具有不同聚合度的萘基-聚(S-((2-羧乙基)硫代)-l-半胱氨酸)肽两亲物：合成、自组装、pH/还原触发的药物释放和细胞毒性

四种具有不同聚合度（DP = 40、15、10 和 6）的肽两亲物 (PA1-4) 通过 Fuchs-Farthing 和开环聚合合成，然后进行聚合后修饰，其完全表征为¹H NMR、FT-IR、凝胶渗透色谱和圆二色谱 (CD) 光谱。发现PA在低浓度（约1 mg/mL）水溶液中可自组装形成规则球形胶束，其二级结构含量不同，主要采用无规卷曲构象。PA的水溶性随着DP的增加而增加，多肽链在水中随机伸展，β-折叠减少，无规卷曲构象占主导地位。当PA溶液的pH降低或升高时，分子内氢键断裂，分子链拉伸，导致α-螺旋减少，构象转变，β-折叠增加。同时，胶束的粒径增大。在 0.4 mg/mL 左右，PA2 的溶血能力在 pH 7.4 和 6.5 时可忽略不计，在 pH 5.5 时约为 33%。顺铂 (CDDP) 通过配位键与胶束相连，以探索它们作为药物载体的潜力，表现出可控的 pH 值和双重药物释放效应的降低。MTT法显示，在13.5 μg/mL PA2空白胶束中培养2天的HeLa细胞活力为78%，而在载有CDDP的胶束中细胞活力为60%。此外，高浓度的 PA2（约 100 mg/mL）可以在 pH 5.5 下自组装成纤维水凝胶，在切开后 2 小时自愈，并在 14 天内自降解 71%。载有 CDDP 的纤维水凝胶表现出与载有 CDDP 的胶束相似的缓释效果。经检测，载CDDP纤维在48 h时的细胞毒性与等量CDDP相同，细胞活力为7%。所以，