Abstract This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and targeting of PTX. K237 peptide was conjugated to the terminal NHS of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)-(DSPE-PEG-NHS), and K237-modified PTX-TSL (K237-PTX-TSL) was prepared using a film dispersion method. K237-TSL encapsulation with calcein was synthesized and used to determine the cellular uptake of TSL. The morphology of K237-PTX-TSL was observed using a transmission electron microscope. The particle size and potential were measured using a laser particle size analyzer. The phase transition temperature was detected using the differential scanning calorimetry. The Cell Counting Kit-8 assay and flow cytometry were used to evaluate the effects of K237-PTX-TSL on the proliferation and cell cycle of cell lines SKOV-3 and human umbilical vein endothelial cell (HUVEC). The encapsulation efficiency of K237-PTX-TSL was 94.23% ± 0.76%. The particle diameter was 88.3 ± 4.7 nm. K237-PTX-TSL showed a fast release profile at 42 °C, while it was stable at 37 °C. PTX-TSL combined with hyperthermia significantly inhibited the cell proliferation of SKOV-3 cells and HUVECs due to increased cell arrest in the G2/M phase. The half-minimal inhibitory concentration value of K237-PTX-TSL on SKOV-3 cells and HUVECs was 13.61 ± 1.81 and 5.54 ± 0.95 nmol/L, respectively, which were significantly lower than those with PTX-TSL (p < 0.01). K237 modification could increase the targeting efficiency of TSL to cancer cells and vascular endothelial cells, thus resulting in higher cytotoxicities compared with PTX-TSL, which might be a potential formulation for targeting cancer therapy.

中文翻译：

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K237修饰的热敏脂质体增强紫杉醇的体外递送效率和细胞毒性

摘要 本研究旨在开发新型负载紫杉醇的温度敏感脂质体（PTX-TSL）并对其进行体外评估，以提高PTX的递送效率和靶向性。K237 肽与 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[羟基琥珀酰亚胺（聚乙二醇）-（DSPE-PEG-NHS）和 K237 修饰的 PTX-TSL（K237 -PTX-TSL) 使用薄膜分散法制备。用钙黄绿素包裹的 K237-TSL 被合成并用于测定 TSL 的细胞摄取。使用透射电子显微镜观察 K237-PTX-TSL 的形态。使用激光粒度分析仪测量粒度和电位。使用差示扫描量热法检测相变温度。Cell Counting Kit-8 检测和流式细胞术用于评估 K237-PTX-TSL 对细胞系 SKOV-3 和人脐静脉内皮细胞 (HUVEC) 增殖和细胞周期的影响。K237-PTX-TSL 的包封率为 94.23% ± 0.76%。粒径为88.3±4.7nm。K237-PTX-TSL 在 42 °C 下显示出快速释放曲线，而在 37 °C 下稳定。PTX-TSL 联合热疗可显着抑制 SKOV-3 细胞和 HUVECs 的细胞增殖，原因是 G2/M 期细胞停滞增加。K237-PTX-TSL 对 SKOV-3 细胞和 HUVECs 的半最低抑制浓度值分别为 13.61±1.81 和 5.54±0.95 nmol/L，显着低于 PTX-TSL（p < 0.01）。