College of Biomedical Engineering, Sichuan University, Chengdu 610065, PR China.
Curr Drug Deliv. 2022 Aug 6;19(9):940-948. doi: 10.2174/1567201819666220321110812.
Liposomes have been widely used in drug delivery systems because the encapsulation of liposomes changes the biological distribution profile and improves the therapeutic indices of various drugs. Thermosensitive liposomes have been proven to be a precise and effective method for cancer therapy in many preclinical studies. However, the lack of specific targeting ability to cancer cells limited their application in safe and efficient chemotherapy.
In the present study, an ovarian targeting ligand namely WSGFPGVWGASVK (WSG) screened by phage display in vivo was grafted on the thermosensitive phospholipids to prepare the liposomes targeting ovarian cancer cells. WSG was first grafted onto the hydrophilic terminal of DSPEPEG2000 molecules, and then the WSG modified thermosensitive liposomes (WSG-Lipo) were prepared by thin-film hydration method. Doxorubicin hydrochloride (DOX) was used as a model drug to investigate the drug release behavior of liposomes at different temperatures. The specificity of liposomes to SKOV-3 cells was studied by cell uptake in vitro.
The WSG-Lipo-DOX could release more DOX at 42°C than at 37°C, showing stronger specificity to SKOV-3 cells and thus selectively inhibiting SKOV-3 cells activity in vitro.
The active targeting liposome showed potential in improving the specificity of thermosensitive liposomes and would be applied in the chemotherapy combined with a thermotherapy.
脂质体由于其改变了药物的生物分布特征并提高了各种药物的治疗指数，因此被广泛应用于药物传递系统中。热敏脂质体已被证明是许多临床前研究中癌症治疗的一种精确而有效的方法。然而，由于缺乏对癌细胞的特异性靶向能力，限制了其在安全有效的化疗中的应用。
在本研究中，通过体内噬菌体展示筛选出一种卵巢靶向配体 WSGFPGVWGASVK（WSG），并将其接枝到热敏磷脂上，制备靶向卵巢癌细胞的脂质体。WSG 首先接枝到 DSPEPEG2000 分子的亲水端，然后通过薄膜水化法制备 WSG 修饰的热敏脂质体（WSG-Lipo）。盐酸多柔比星（DOX）被用作模型药物，以研究脂质体在不同温度下的药物释放行为。通过体外细胞摄取研究了脂质体对 SKOV-3 细胞的特异性。
WSG-Lipo-DOX 在 42°C 时比在 37°C 时释放更多的 DOX，对 SKOV-3 细胞表现出更强的特异性，从而选择性地抑制 SKOV-3 细胞的体外活性。
主动靶向脂质体显示出提高热敏脂质体特异性的潜力，将应用于与热疗相结合的化疗中。
