Hebrew University-School of Medicine, Jerusalem, Israel.
Shaare Zedek Medical Center- Oncology Institute, Jerusalem, Israel.
Nanomedicine. 2018 Jun;14(4):1407-1416. doi: 10.1016/j.nano.2018.04.011. Epub 2018 Apr 19.
Folate-targeted liposomes (FTL) were tested as drug delivery vehicles to PSMA-positive cancer cells. We used FL with co-entrapped mitomycin C lipophilic prodrug (MLP) and doxorubicin (DOX), and the LNCaP prostate cancer cell line which expresses PSMA but is negative for folate receptor. A major increase in cell drug levels was observed when LNCaP cells were incubated with FTL as compared to non-targeted liposomes (NTL). MLP was activated to mitomycin C, and intracellular and nuclear fluorescence of DOX was detected, indicating FTL processing and drug bioavailability. PMPA (2-(phosphonomethyl)-pentanedioic acid), a specific inhibitor of PSMA, blocked the uptake of FTL into LNCaP cells, but did not affect the uptake of FTL into PSMA-deficient and folate receptor-positive KB cells. The cytotoxic activity of drug-loaded FTL was found significantly enhanced when compared to NTL in LNCaP cells. FTL may provide a new tool for targeted therapy of cancers that over-express the PSMA receptor.
叶酸靶向脂质体（FTL）被测试为 PSMA 阳性癌细胞的药物递送载体。我们使用了共包封丝裂霉素 C 亲脂前药（MLP）和阿霉素（DOX）的 FL，以及表达 PSMA 但缺乏叶酸受体的 LNCaP 前列腺癌细胞系。与非靶向脂质体（NTL）相比，当 LNCaP 细胞用 FTL 孵育时，观察到细胞内药物水平显著增加。MLP 被激活为丝裂霉素 C，并检测到 DOX 的细胞内和核荧光，表明 FTL 的处理和药物生物利用度。PMPA（2-（膦酸甲基）戊二酸）是 PSMA 的特异性抑制剂，可阻止 FTL 进入 LNCaP 细胞，但不影响 PSMA 缺乏和叶酸受体阳性 KB 细胞对 FTL 的摄取。与 LNCaP 细胞中的 NTL 相比，载药 FTL 的细胞毒性活性显著增强。FTL 可能为过度表达 PSMA 受体的癌症的靶向治疗提供新工具。
