Sacchetti Francesca, Marraccini Chiara, D'Arca Domenico, Pelà Michela, Pinetti Diego, Maretti Eleonora, Hanuskova Miriam, Iannuccelli Valentina, Costi Maria Paola, Leo Eliana
Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy.
Department of Biomedical, Metabolical and Neural Sciences University of Modena and Reggio Emilia, via Campi 287, 41125 Modena, Italy.
Colloids Surf B Biointerfaces. 2015 Dec 1;136:346-54. doi: 10.1016/j.colsurfb.2015.09.040. Epub 2015 Sep 25.
Recently, octapeptide LSCQLYQR (LRp), reducing growth of cis-platinum (cDDP) resistant ovarian carcinoma cells by inhibiting the monomer-monomer interface of the human enzyme thymidylate synthase, has been identified. As the peptide is not able to cross the cell membrane it requires an appropriate delivery system. In this work the application of SLNs, biocompatible and efficient tools for the intracellular drug transport, applied especially for lipophilic drugs, was exploited for the delivery of the hydrophilic peptide LRp. SLNs formulated in the absence/presence of small amount of squalene showed dimensions below 150 nm, negative zeta potential and good stability to the freeze-drying process. Even though the particles formulated with squalene exhibited a less ordered crystal lattice and a lower surface hydrophobicity, a rapid drug release from these nanocarriers occurred as a result of the relevant expulsion of the drug from the lipid core during lipid crystallization. On the contrary, SLNs formulated in the absence of squalene were able to incorporate more stably the peptide showing considerable cytotoxic effect on cDDP resistant C13* ovarian carcinoma cell line at concentration 50 times lower than that used previously with a marketed delivery system. From the cell cycle analysis by the propidium iodide test in SLNs-peptide treated cancer cells an increase of apoptosis percentage was observed, indicating that SLNs were able to carry efficiently the peptide until its enzymatic target.
最近，已鉴定出八肽LSCQLYQR（LRp），它通过抑制人胸苷酸合成酶的单体 - 单体界面来降低顺铂（cDDP）耐药卵巢癌细胞的生长。由于该肽无法穿过细胞膜，因此需要合适的递送系统。在这项工作中，利用了固体脂质纳米粒（SLNs），这是一种用于细胞内药物运输的生物相容性良好且高效的工具，尤其适用于亲脂性药物，来递送亲水性肽LRp。在不存在/存在少量角鲨烯的情况下制备的SLNs显示尺寸低于150nm，具有负的zeta电位，并且对冷冻干燥过程具有良好的稳定性。尽管用角鲨烯制备的颗粒表现出较无序的晶格和较低的表面疏水性，但由于在脂质结晶过程中药物从脂质核心的相关排出，这些纳米载体中出现了快速的药物释放。相反，在不存在角鲨烯的情况下制备的SLNs能够更稳定地包载该肽，在浓度比先前使用市售递送系统时低50倍的情况下，对cDDP耐药的C13*卵巢癌细胞系显示出相当大的细胞毒性作用。通过碘化丙啶试验对经SLNs - 肽处理的癌细胞进行细胞周期分析，观察到凋亡百分比增加，表明SLNs能够有效地携带该肽直至其酶作用靶点。
