Cargando…

Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer

As a natural compound, gambogic acid (GA) emerged a shining multi-target antitumor activity in a variety of tumors. Whereas its poor solubility and non-specific effect to tumor blocked the clinical application of this drug. Herein, we reported a simple and effective strategy to construct liposome mo...

Descripción completa

Detalles Bibliográficos
Autores principales: Dang, Wenli, Guo, Pan, Song, Xunan, Zhang, Ying, Li, Nan, Yu, Changxiang, Xing, Bin, Liu, Rui, Jia, Xintao, Zhang, Qingqing, Feng, Xiaojiao, Liu, Zhidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832139/
https://www.ncbi.nlm.nih.gov/pubmed/35155383
http://dx.doi.org/10.3389/fchem.2021.821426
_version_ 1784648662282928128
author Dang, Wenli
Guo, Pan
Song, Xunan
Zhang, Ying
Li, Nan
Yu, Changxiang
Xing, Bin
Liu, Rui
Jia, Xintao
Zhang, Qingqing
Feng, Xiaojiao
Liu, Zhidong
author_facet Dang, Wenli
Guo, Pan
Song, Xunan
Zhang, Ying
Li, Nan
Yu, Changxiang
Xing, Bin
Liu, Rui
Jia, Xintao
Zhang, Qingqing
Feng, Xiaojiao
Liu, Zhidong
author_sort Dang, Wenli
collection PubMed
description As a natural compound, gambogic acid (GA) emerged a shining multi-target antitumor activity in a variety of tumors. Whereas its poor solubility and non-specific effect to tumor blocked the clinical application of this drug. Herein, we reported a simple and effective strategy to construct liposome modified with nuclear targeted peptide CB5005N (VQRKRQKLMPC) via polyethylene glycol (PEG) linker to decrease the inherent limitations of GA and promote its anti-tumor activity. In this study, liposomes were prepared by thin film hydration method. The characterization of formulations contained particle size, Zeta potential, morphology and encapsulation efficiency. Further, in vitro cytotoxicity and uptake tests were investigated by 4T1 and MDA-MB-231 cells, and nuclear targeting capability was performed on MDA-MB-231 cells. In addition, the in vivo antitumor effect and biological distribution of formulations were tested in BALB/c female mice. The GA-loaded liposome modified by CB5005N showed small size, good uniformity, better targeting, higher anti-tumor efficiency, better tumor inhibition rate and lower toxicity to normal tissues than other groups. In vitro and in vivo research proved that CB5005N-GA-liposome exhibited excellent anti-tumor activity and significantly reduced toxicities. As a result, CB5005N-GA-liposome nano drug delivery system enhanced the tumor targeting and antitumor effects of GA, which provided a basis for its clinical application.
format Online
Article
Text
id pubmed-8832139
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-88321392022-02-12 Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer Dang, Wenli Guo, Pan Song, Xunan Zhang, Ying Li, Nan Yu, Changxiang Xing, Bin Liu, Rui Jia, Xintao Zhang, Qingqing Feng, Xiaojiao Liu, Zhidong Front Chem Chemistry As a natural compound, gambogic acid (GA) emerged a shining multi-target antitumor activity in a variety of tumors. Whereas its poor solubility and non-specific effect to tumor blocked the clinical application of this drug. Herein, we reported a simple and effective strategy to construct liposome modified with nuclear targeted peptide CB5005N (VQRKRQKLMPC) via polyethylene glycol (PEG) linker to decrease the inherent limitations of GA and promote its anti-tumor activity. In this study, liposomes were prepared by thin film hydration method. The characterization of formulations contained particle size, Zeta potential, morphology and encapsulation efficiency. Further, in vitro cytotoxicity and uptake tests were investigated by 4T1 and MDA-MB-231 cells, and nuclear targeting capability was performed on MDA-MB-231 cells. In addition, the in vivo antitumor effect and biological distribution of formulations were tested in BALB/c female mice. The GA-loaded liposome modified by CB5005N showed small size, good uniformity, better targeting, higher anti-tumor efficiency, better tumor inhibition rate and lower toxicity to normal tissues than other groups. In vitro and in vivo research proved that CB5005N-GA-liposome exhibited excellent anti-tumor activity and significantly reduced toxicities. As a result, CB5005N-GA-liposome nano drug delivery system enhanced the tumor targeting and antitumor effects of GA, which provided a basis for its clinical application. Frontiers Media S.A. 2022-01-28 /pmc/articles/PMC8832139/ /pubmed/35155383 http://dx.doi.org/10.3389/fchem.2021.821426 Text en Copyright © 2022 Dang, Guo, Song, Zhang, Li, Yu, Xing, Liu, Jia, Zhang, Feng and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Dang, Wenli
Guo, Pan
Song, Xunan
Zhang, Ying
Li, Nan
Yu, Changxiang
Xing, Bin
Liu, Rui
Jia, Xintao
Zhang, Qingqing
Feng, Xiaojiao
Liu, Zhidong
Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer
title Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer
title_full Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer
title_fullStr Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer
title_full_unstemmed Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer
title_short Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer
title_sort nuclear targeted peptide combined with gambogic acid for synergistic treatment of breast cancer
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832139/
https://www.ncbi.nlm.nih.gov/pubmed/35155383
http://dx.doi.org/10.3389/fchem.2021.821426
work_keys_str_mv AT dangwenli nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT guopan nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT songxunan nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT zhangying nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT linan nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT yuchangxiang nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT xingbin nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT liurui nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT jiaxintao nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT zhangqingqing nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT fengxiaojiao nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer
AT liuzhidong nucleartargetedpeptidecombinedwithgambogicacidforsynergistictreatmentofbreastcancer