Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro
Guang-Hua Xiang,1,2,* Guo-Bin Hong,2,3,* Yong Wang,2 Du Cheng,2 Jing-Xing Zhou,1 Xin-Tao Shuai21Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical E...
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Dove Medical Press
2013
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oai:doaj.org-article:39f07a01a3ef4dd3b4776495fcc931a52021-12-02T01:35:22ZEffect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro1176-91141178-2013https://doaj.org/article/39f07a01a3ef4dd3b4776495fcc931a52013-12-01T00:00:00Zhttp://www.dovepress.com/effect-of-peg-pdlla-polymeric-nanovesicles-loaded-with-doxorubicin-and-a15140https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Guang-Hua Xiang,1,2,* Guo-Bin Hong,2,3,* Yong Wang,2 Du Cheng,2 Jing-Xing Zhou,1 Xin-Tao Shuai21Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China; 3Department of Radiology, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, People's Republic of China*These two authors contributed equally to this workObjective: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: polymeric vesicles, hematoporphyrin monomethyl ether, HMME, photodynamic therapy, PDTXiang GHHong GBWang YCheng DZhou JXShuai XTDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss Issue 1, Pp 4613-4622 (2013) |
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Medicine (General) R5-920 Xiang GH Hong GB Wang Y Cheng D Zhou JX Shuai XT Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro |
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Guang-Hua Xiang,1,2,* Guo-Bin Hong,2,3,* Yong Wang,2 Du Cheng,2 Jing-Xing Zhou,1 Xin-Tao Shuai21Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China; 3Department of Radiology, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, People's Republic of China*These two authors contributed equally to this workObjective: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: polymeric vesicles, hematoporphyrin monomethyl ether, HMME, photodynamic therapy, PDT |
format |
article |
author |
Xiang GH Hong GB Wang Y Cheng D Zhou JX Shuai XT |
author_facet |
Xiang GH Hong GB Wang Y Cheng D Zhou JX Shuai XT |
author_sort |
Xiang GH |
title |
Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro |
title_short |
Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro |
title_full |
Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro |
title_fullStr |
Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro |
title_full_unstemmed |
Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro |
title_sort |
effect of peg-pdlla polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma hepg2 cells in vitro |
publisher |
Dove Medical Press |
publishDate |
2013 |
url |
https://doaj.org/article/39f07a01a3ef4dd3b4776495fcc931a5 |
work_keys_str_mv |
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