Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China ; PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Int J Nanomedicine. 2013;8:4613-22. doi: 10.2147/IJN.S54142. Epub 2013 Dec 2.
To evaluate the cytotoxicity of poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles loaded with doxorubicin (DOX) and the photosensitizer hematoporphyrin monomethyl ether (HMME) on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms.
PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME), and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX), HMME (PEG-PDLLA-HMME), or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined.
Four nanovesicles (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA) were synthesized, and mean particle sizes were 175±18 nm, 154±3 nm, 196±2 nm, and 147±15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar fluorescence intensity. Mitochondrial membrane potential depolarization was observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with PEG-PDLLA-DOX-HMME, PEG-PDLLA-HMME, PEG-PDLLA-DOX, and PEG-PDLLA, respectively. The apoptotic rate was significantly higher in PEG-PDLLA-DOX-HMME-treated cells compared with PEG-PDLLA-DOX- and PEG-PDLLA-HMME-treated cells.
The PEG-PDLLA nanovesicle, a drug delivery carrier, can be simultaneously loaded with two anticancer drugs (hydrophilic DOX and hydrophobic HMME). PEG-PDLLA-DOX-HMME cytotoxicity to HepG2 cells is significantly higher than the PEG-PDLLA nanovesicle loaded with DOX or HMME alone, and DOX and HMME have a synergistic effect against human hepatocellular carcinoma HepG2 cells.
评价载多柔比星（DOX）和血卟啉单甲醚（HMME）的聚乙二醇-嵌段-聚（D，L-乳酸）（PEG-PDLLA）纳米囊泡对人肝癌 HepG2 细胞的细胞毒性，并探讨其潜在的凋亡机制。
将 DOX 和 HMME 同时载入 PEG-PDLLA 纳米囊泡（PEG-PDLLA-DOX-HMME）中，同时将 DOX 载入 PEG-PDLLA 纳米囊泡（PEG-PDLLA-DOX）、HMME 载入 PEG-PDLLA 纳米囊泡（PEG-PDLLA-HMME）或单独载入 PEG-PDLLA 纳米囊泡作为对照。测量 PEG-PDLLA-DOX-HMME、PEG-PDLLA-DOX、PEG-PDLLA-HMME 和 PEG-PDLLA 对 HepG2 细胞的细胞毒性，并测定细胞内活性氧、线粒体膜电位去极化的细胞百分比和处理后的细胞凋亡率。
合成了 4 种纳米囊泡（PEG-PDLLA-DOX-HMME、PEG-PDLLA-DOX、PEG-PDLLA-HMME 和 PEG-PDLLA），平均粒径分别为 175±18nm、154±3nm、196±2nm 和 147±15nm。PEG-PDLLA-DOX-HMME 比 PEG-PDLLA-DOX、PEG-PDLLA-HMME 和 PEG-PDLLA 更具细胞毒性。PEG-PDLLA-HMME 处理的细胞平均荧光强度最高，其次是 PEG-PDLLA-DOX-HMME 处理的细胞，而 PEG-PDLLA-DOX 和 PEG-PDLLA 处理的细胞荧光强度相似。PEG-PDLLA-DOX-HMME、PEG-PDLLA-HMME、PEG-PDLLA-DOX 和 PEG-PDLLA 处理的细胞中，线粒体膜电位去极化分别为 54.2%、59.4%、13.8%和 14.8%。与 PEG-PDLLA-DOX 和 PEG-PDLLA-HMME 处理的细胞相比，PEG-PDLLA-DOX-HMME 处理的细胞凋亡率显著更高。
PEG-PDLLA 纳米囊泡作为一种药物载体，可同时载入两种抗癌药物（亲水性 DOX 和疏水性 HMME）。PEG-PDLLA-DOX-HMME 对 HepG2 细胞的细胞毒性明显高于单独载入 DOX 或 HMME 的 PEG-PDLLA 纳米囊泡，且 DOX 和 HMME 对人肝癌 HepG2 细胞具有协同作用。
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