Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Colloids Surf B Biointerfaces. 2021 Apr;200:111589. doi: 10.1016/j.colsurfb.2021.111589. Epub 2021 Jan 22.
Employing targeting ligands on the surface of liposomes has the great potential to improve therapeutic efficacy and decreases off-target effects of liposomal formulations. In the present study, a leptin-derived peptide (Lp31) was evaluated to optimize the therapeutic efficacy of PEGylated liposomal Doxorubicin (PLD, Caelyx®). Leptin is an appetite regulatory hormone that is secreted into the blood circulation by the adipose tissue and it functions via its over expressed receptors (Ob-R) in a wide variety of cancers. Lp31, as targeting ligand, was conjugated to Maleimide-PEG2000-DSPE and then post-inserted into Caelyx. The anti-tumor activity and therapeutic efficacy of leptin modified Caelyx were evaluated and compared with Caelyx. The in vitro experiments demonstrated enhanced cytotoxicity and cellular uptake of Lp31-targeted Caelyx in C26 cell line compared to Caelyx. In BALB/c mice bearing C-26 murine carcinoma, Lp31 modified Caelyx groups exhibited significantly higher doxorubicin concentration at tumor tissue. Furthermore, Lp31 modified Caelyx at the dose of 10 mg/kg resulted in significant tumor growth inhibition and enhanced survival time compared to Caelyx. According to these results, the novel Lp31-liposomal doxorubicin offers great promise for the treatment of colon cancer and merits further investigation.
在脂质体表面使用靶向配体具有极大的潜力，可以提高治疗效果并降低脂质体制剂的脱靶效应。在本研究中，评估了瘦素衍生肽（Lp31）以优化聚乙二醇化脂质体多柔比星（PLD，Caelyx®）的治疗效果。瘦素是一种食欲调节激素，由脂肪组织分泌到血液循环中，并通过其在各种癌症中过度表达的受体（Ob-R）发挥作用。Lp31 作为靶向配体，与马来酰亚胺-PEG2000-DSPE 缀合，然后插入 Caelyx 中。评价了并比较了 Lp31 修饰的 Caelyx 的抗肿瘤活性和治疗效果。与 Caelyx 相比，体外实验表明，Lp31 靶向 Caelyx 在 C26 细胞系中具有增强的细胞毒性和细胞摄取。在携带 C-26 鼠肉瘤的 BALB/c 小鼠中，Lp31 修饰的 Caelyx 组在肿瘤组织中表现出更高的阿霉素浓度。此外，与 Caelyx 相比，10mg/kg 剂量的 Lp31 修饰的 Caelyx 导致显著的肿瘤生长抑制和延长的存活时间。根据这些结果，新型 Lp31-脂质体阿霉素为治疗结肠癌提供了巨大的前景，值得进一步研究。
