Active loading of verteporfin into cationic liposome for neovasculature- and tumor-targeted photodynamic therapy
10.16438/j.0513-4870.2020-0661
- VernacularTitle:主动包载维替泊芬阳离子脂质体用于新生血管和肿瘤靶向光动力治疗
- Author:
Fang-jie WAN
1
;
Bin-long CHEN
1
;
Lin-jie YANG
1
;
Qing-qing YIN
1
;
Yue YAN
1
;
Ye YANG
1
;
Qiang ZHANG
1
;
Yi-guang WANG
1
Author Information
1. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
- Publication Type:Research Article
- Keywords:
cationic liposome;
neovascular targeting;
tumor targeting;
photodynamic therapy;
verteporfin;
calcium acetate gradient method
- From:
Acta Pharmaceutica Sinica
2020;55(7):1680-1690
- CountryChina
- Language:Chinese
-
Abstract:
To target neovasculature and tumor cells, a novel cationic liposome with verteporfin (BPD) active-loaded in lumen (CLL) was designed and its basic in vitro and in vivo behaviors were evaluated in this study. Calcium acetate gradient loading method was applied to encapsulate BPD actively and cationic lipid (2,3-dioleoy-loxy-propyl)-trimethylammonium (DOTAP) was added by post-insertion for the positive charge of CLL. Results of characterization showed that the diameter and zeta-potential of CLL were around 100 nm and 28 mV, respectively. Compared with passive loading liposomes, CLL significantly enhanced the stability of BPD loading. What's more, the loaded BPD in lumen could switch off the fluorescence and photosensitization during blood circulation by homo-fluorescence resonance energy transfer (homo-FRET) effect, leading to the diminished phototoxicity to normal tissues. In vitro cellular uptake and cytotoxicity assay exhibited that positive charge dramatically enhanced the uptake of CLL both in vascular endothelial cells and tumor cells leading to superior therapeutic efficacy. In vivo study further showed that CLL reduced the clearance rate and increased tumor accumulation compared with passive loading group. Quantitative results of exvivo organ indicated that negligible CLL distributed in normal organs contributing to low phototoxicity. Animal experiments were conducted according to the Guidelines of the Experimental Animal Ethics Committee of Peking University Health Science Center and International Animal Experiments. In conclusion, we successfully designed a novel cationic targeting liposome that overcame the limitations of passive loading and significantly enhanced the efficacy of photodynamic therapy.
