Huaiyu Tong1, Yan Wang2, Xuechun Lu3, Peng Wang1, Shupeng Zhao4, Haigang Chang4, Xinguang Yu1. 1. Department of Neurosurgery, PLA General Hospital Beijing 100853, China. 2. Department of Neurosurgery, The First Affiliated Hospital of PLA General Hospital Beijing 100853, China. 3. Department of Hematology, PLA General Hospital Beijing 100853, China. 4. Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
Abstract
OBJECTIVE: To prepare transferrin modified artesunate nanoliposomes (Tf-ART-LPs) and study their glioma U87 cells-targeting treatment in-vitro and in-vivo. METHODS: Ammonium sulfate transmembrane gradient method was used to prepare Tf-ART-LPs, whose size and stability was detected by a Nanosizer. Besides, the encapsulation efficiency and release rate of artesunate (ART) were tested by a ultraviolet spectrophotometer. Further, isothiocyanate (FITC) was used to label nanoliposomes and the cell-targeting property of Tf-ART-LP in-vitro was observed under a fluorescence microscope. In addition, CCK-8 method was used to detect the effect of single nanoliposomes and Tf-ART-LPs on the viability of glioma U87 cells. At last, a subcutaneously implanted tumor model in nude mouse was established for studying the in-vivo anti-tumor effect of Tf-ART-LPs by caudal vein injection. The tumor volume and mice weight were monitored and pathological sections of their major organs were analyzed. RESULTS: Tf-ART-LPs were spherical with an average diameter of 94.2 nm. They showed no aggregation after being stored in a refrigerator for 14 days at 4°C. The encapsulation efficiency and highest releasing rate (48 hours after being placed in normal saline under 37°C) of ART was 85.9% and 58.7±2.9%, respectively. The uptake rate of U87 cells was 59.8±3.8% for Tf-ART-LPs and only 18.7±4.5% for ART-LPs. While single liposomes almost showed no toxicity, Tf-ART-LP had a concentration-dependent killing effect on U87 cells. Within 32 days of treatment, the growth of U87 cells was well inhibited by Tf-ART-LPs without significant toxicity. CONCLUSION: In this study, transferrin modified artesunate liposomes we prepared have a good targeting property to glioma U87 cells and good effect on glioma both in-vitro and in-vivo.
OBJECTIVE: To prepare transferrin modified artesunate nanoliposomes (Tf-ART-LPs) and study their glioma U87 cells-targeting treatment in-vitro and in-vivo. METHODS:Ammonium sulfate transmembrane gradient method was used to prepare Tf-ART-LPs, whose size and stability was detected by a Nanosizer. Besides, the encapsulation efficiency and release rate of artesunate (ART) were tested by a ultraviolet spectrophotometer. Further, isothiocyanate (FITC) was used to label nanoliposomes and the cell-targeting property of Tf-ART-LP in-vitro was observed under a fluorescence microscope. In addition, CCK-8 method was used to detect the effect of single nanoliposomes and Tf-ART-LPs on the viability of glioma U87 cells. At last, a subcutaneously implanted tumor model in nude mouse was established for studying the in-vivo anti-tumor effect of Tf-ART-LPs by caudal vein injection. The tumor volume and mice weight were monitored and pathological sections of their major organs were analyzed. RESULTS: Tf-ART-LPs were spherical with an average diameter of 94.2 nm. They showed no aggregation after being stored in a refrigerator for 14 days at 4°C. The encapsulation efficiency and highest releasing rate (48 hours after being placed in normal saline under 37°C) of ART was 85.9% and 58.7±2.9%, respectively. The uptake rate of U87 cells was 59.8±3.8% for Tf-ART-LPs and only 18.7±4.5% for ART-LPs. While single liposomes almost showed no toxicity, Tf-ART-LP had a concentration-dependent killing effect on U87 cells. Within 32 days of treatment, the growth of U87 cells was well inhibited by Tf-ART-LPs without significant toxicity. CONCLUSION: In this study, transferrin modified artesunate liposomes we prepared have a good targeting property to glioma U87 cells and good effect on glioma both in-vitro and in-vivo.
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