Yang Yanfang, Xie Xiangyang, Yang Yang, Zhang Hui, Mei Xingguo
Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical college, Beijing, 100050, China.
J Pharm Sci. 2015 Apr;104(4):1328-39. doi: 10.1002/jps.24333. Epub 2015 Jan 28.
A novel nanostructured lipid carrier (NLC) modified with photon-sensitive cell penetrating peptides (psCPP) and Asn-Gly-Arg (NGR) was designed to enhance paclitaxel (PTX)-targeted delivery and antitumor effect. The NGR moiety selectively binds to CD13-positive tumors. On other hand, the psCPP moiety enhance specific cancer cellular uptake after rapidly cleaving the two-photon excitation-responsive protective group, in this case, illumination in the presence of near-IR (NIR) light at the tumor site. The dual-modified NLC (psCPP/NGR-NLC) were prepared by emulsification method, and the concentrations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol 2000-psCPP (DSPE-PEG2000 -psCPP) and DSPE-PEG5000 -NGR in the NLC were chosen to be 4% and 1% (molar ratio), respectively. The mean particle size of the psCPP/NGR-NLC was about 100 nm, and the drug entrapment efficiency was more than 90%. Stability study showed that the prepared NLCs were physically and chemically stable at 2°C-8°C up to 1 month. Cellular uptake results demonstrated that the proposed psCPP/NGR-NLC had an enhancement of cancer cell recognition and specific uptake. Pharmacokinetic study showed that the prepared psCPP/NGR-NLC possessed the long-circulation characteristic with the t1/2 of 6.112 ± 0.304 h. Pharmacodynamics results confirmed that, with the aid of NIR illumination and NGR, the tumor inhibition ratio of psCPP/NGR-NLC group was significantly higher than the other PTX groups.
设计了一种用光子敏感细胞穿透肽（psCPP）和天冬酰胺-甘氨酸-精氨酸（NGR）修饰的新型纳米结构脂质载体（NLC），以增强紫杉醇（PTX）的靶向递送和抗肿瘤效果。NGR部分选择性结合CD13阳性肿瘤。另一方面，psCPP部分在快速切割双光子激发响应保护基团后增强特定癌细胞摄取，在这种情况下，在肿瘤部位近红外（NIR）光照射下进行。通过乳化法制备双修饰NLC（psCPP/NGR-NLC），NLC中1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-聚乙二醇2000-psCPP（DSPE-PEG2000-psCPP）和DSPE-PEG5000-NGR的浓度分别选择为4%和1%（摩尔比）。psCPP/NGR-NLC的平均粒径约为100nm，药物包封率超过90%。稳定性研究表明，制备的NLC在2°C-8°C下物理和化学稳定长达1个月。细胞摄取结果表明，所提出的psCPP/NGR-NLC增强了癌细胞识别和特异性摄取。药代动力学研究表明，制备的psCPP/NGR-NLC具有长循环特性，t1/2为6.112±0.304h。药效学结果证实，借助NIR照射和NGR，psCPP/NGR-NLC组的肿瘤抑制率显著高于其他PTX组。
