The Key Laboratory of Breast Cancer Prevention and Therapy Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
Pharm Res. 2010 Sep;27(9):1914-26. doi: 10.1007/s11095-010-0196-5. Epub 2010 Jun 26.
Folic acid and TAT peptide were conjugated on the octadecyl-quaternized, lysine-modified chitosan-cholesterol polymeric liposomes (FA-TATp-PLs) to investigate their potential feasibility for tumor-targeted drug delivery.
FA-TATp-PLs encapsulating paclitaxel or calcein were synthesized and characterized. Cellular uptake of PLs, FA-PLs, TATp-PLs and FA-TATp-PLs was studied by confocal laser scanning microscopy (CLSM) in folate receptor (FR)-positive KB nasopharyngeal epidermal carcinoma cells and FR-deficient A549 lung cancer cells. In vitro and in vivo antitumor activity of paclitaxel-loaded FA-TATp-PLs were also evaluated in KB and A549 cells as well as in a murine KB xenograft model.
Our data showed that 80% paclitaxel released from FA-TATp-PLs in 2 weeks. Different from other various PLs, CLSM analyses showed that FA-TATp-PLs had a significantly high efficient intracellular uptake in both KB and A549 cells. These data revealed the targeting effects of folate decoration, the transmembrane ability of TAT peptide as well as a synergistic interaction between them. In addition, paclitaxel-loaded FA-TATp-PLs exhibited a more superior antitumor effect in vitro and in vivo as compared to that with Taxol.
FA-TATp-PLs possessing both targeting effect and transmembrane ability may serve as a promising carrier for the intracellular delivery of therapeutic agents.
将叶酸和 TAT 肽偶联到十八烷基季铵化、赖氨酸修饰的壳聚糖-胆固醇聚合物脂质体(FA-TATp-PLs)上,以研究其用于肿瘤靶向药物传递的潜在可行性。
合成并表征了包载紫杉醇或钙黄绿素的 FA-TATp-PLs。通过共聚焦激光扫描显微镜(CLSM)研究了 FA-TATp-PLs、FA-PLs、TATp-PLs 和 FA-TATp-PLs 在叶酸受体(FR)阳性 KB 鼻咽表皮癌细胞和 FR 缺失的 A549 肺癌细胞中的细胞摄取情况。还在 KB 和 A549 细胞以及小鼠 KB 异种移植模型中评估了载紫杉醇的 FA-TATp-PLs 的体外和体内抗肿瘤活性。
我们的数据表明,FA-TATp-PLs 在 2 周内释放了 80%的紫杉醇。与其他各种 PLs 不同,CLSM 分析表明,FA-TATp-PLs 在 KB 和 A549 细胞中均具有高效的细胞内摄取。这些数据揭示了叶酸修饰的靶向作用、TAT 肽的跨膜能力以及它们之间的协同相互作用。此外,与 Taxol 相比,载紫杉醇的 FA-TATp-PLs 在体外和体内均表现出更优异的抗肿瘤效果。
具有靶向作用和跨膜能力的 FA-TATp-PLs 可能成为治疗剂细胞内递药的有前途的载体。