Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma

Glioma is one of the most aggressive and common malignant brain tumors. Due to the presence of the blood-brain barrier (BBB), the effectiveness of therapeutics is greatly affected. In this work, to develop an efficient anti-glioma drug with targeting and which was able to cross the BBB, cell-penetra...

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Main Authors: Xi Wang, Yarong Zhao, Shiyan Dong, Robert J. Lee, Dongsheng Yang, Huan Zhang, Lesheng Teng
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/24/19/3540
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author Xi Wang
Yarong Zhao
Shiyan Dong
Robert J. Lee
Dongsheng Yang
Huan Zhang
Lesheng Teng
author_facet Xi Wang
Yarong Zhao
Shiyan Dong
Robert J. Lee
Dongsheng Yang
Huan Zhang
Lesheng Teng
author_sort Xi Wang
collection DOAJ
description Glioma is one of the most aggressive and common malignant brain tumors. Due to the presence of the blood-brain barrier (BBB), the effectiveness of therapeutics is greatly affected. In this work, to develop an efficient anti-glioma drug with targeting and which was able to cross the BBB, cell-penetrating peptides (R8) and transferrin co-modified doxorubicin (DOX)-loaded liposomes (Tf-LPs) were prepared. Tf-LPs possessed a spherical shape and uniform size with 128.64 nm and their ξ-potential was 6.81 mV. Tf-LPs were found to be stable in serum within 48 h. Uptake of Tf-LPs in both U87 and GL261 cells was analyzed by confocal laser scanning microscopy and by flow cytometry. Tf-LPs were efficiently taken up by both U87 and GL261 cells. Moreover, Tf-LPs exhibited sustained-release. The cumulative release of DOX from Tf-LPs reached ~50.0% and showed excellent anti-glioma efficacy. Histology of major organs, including brain, heart, liver, spleen, lungs and kidney, and the bodyweight of mice, all indicated low toxicity of Tf-LPs. In conclusion, Tf-LPs showed great promise as an anti-glioma therapeutic agent.
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spelling doaj.art-ec56afd0dbab44a7875ed0fa8d13e7c92022-12-22T03:35:20ZengMDPI AGMolecules1420-30492019-09-012419354010.3390/molecules24193540molecules24193540Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of GliomaXi Wang0Yarong Zhao1Shiyan Dong2Robert J. Lee3Dongsheng Yang4Huan Zhang5Lesheng Teng6School of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaDivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USADepartment of Chemistry and Pharmacy, Zhuhai College of Jilin University, Zhuhai 519041, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaGlioma is one of the most aggressive and common malignant brain tumors. Due to the presence of the blood-brain barrier (BBB), the effectiveness of therapeutics is greatly affected. In this work, to develop an efficient anti-glioma drug with targeting and which was able to cross the BBB, cell-penetrating peptides (R8) and transferrin co-modified doxorubicin (DOX)-loaded liposomes (Tf-LPs) were prepared. Tf-LPs possessed a spherical shape and uniform size with 128.64 nm and their ξ-potential was 6.81 mV. Tf-LPs were found to be stable in serum within 48 h. Uptake of Tf-LPs in both U87 and GL261 cells was analyzed by confocal laser scanning microscopy and by flow cytometry. Tf-LPs were efficiently taken up by both U87 and GL261 cells. Moreover, Tf-LPs exhibited sustained-release. The cumulative release of DOX from Tf-LPs reached ~50.0% and showed excellent anti-glioma efficacy. Histology of major organs, including brain, heart, liver, spleen, lungs and kidney, and the bodyweight of mice, all indicated low toxicity of Tf-LPs. In conclusion, Tf-LPs showed great promise as an anti-glioma therapeutic agent.https://www.mdpi.com/1420-3049/24/19/3540cell-penetrating peptidestargetinggliomablood-brain barrier
spellingShingle Xi Wang
Yarong Zhao
Shiyan Dong
Robert J. Lee
Dongsheng Yang
Huan Zhang
Lesheng Teng
Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma
Molecules
cell-penetrating peptides
targeting
glioma
blood-brain barrier
title Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma
title_full Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma
title_fullStr Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma
title_full_unstemmed Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma
title_short Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma
title_sort cell penetrating peptide and transferrin co modified liposomes for targeted therapy of glioma
topic cell-penetrating peptides
targeting
glioma
blood-brain barrier
url https://www.mdpi.com/1420-3049/24/19/3540
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