Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity

Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity

Xiao-qian Dou,1 Hua Wang,2 Jing Zhang,3 Fang Wang,3 Gui-li Xu,1 Cheng-cheng Xu,1 Huan-hua Xu,1 Shen-si Xiang,1 Jie Fu,1 Hai-feng Song1  1Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China; 2Ophthalmology Department, Eye Hospi...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Dou XQ, Wang H, Zhang J, Wang F, Xu GL, Xu CC, Xu HH, Xiang SS, Fu J, Song HF
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
Breast cancer
human epidermal growth factor receptor 3
aptamer-drug conjugate
doxorubicin
cardiac toxicity
targeted therapy
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/d97216c704854400aacb4cc46a28b3e5
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:d97216c704854400aacb4cc46a28b3e5
record_format dspace
spelling oai:doaj.org-article:d97216c704854400aacb4cc46a28b3e52021-12-02T02:05:00ZAptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity1178-2013https://doaj.org/article/d97216c704854400aacb4cc46a28b3e52018-02-01T00:00:00Zhttps://www.dovepress.com/aptamer-drug-conjugate-targeted-delivery-of-doxorubicin-in-a-her3-apta-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiao-qian Dou,1 Hua Wang,2 Jing Zhang,3 Fang Wang,3 Gui-li Xu,1 Cheng-cheng Xu,1 Huan-hua Xu,1 Shen-si Xiang,1 Jie Fu,1 Hai-feng Song1  1Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China; 2Ophthalmology Department, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China; 3Bioanalysis Department, United-Power Pharma Tech Co., Ltd., Beijing, China Introduction: The toxic side effects of doxorubicin (DOX) have limited its use in chemotherapy. Neither liposomal DOX nor pegylated liposomal DOX are able to completely resolve this issue. This is a proof-of-concept study testing aptamer-drug conjugate (ApDC) targeted delivery systems for chemotherapeutic drugs.Methods: Aptamer library targeting human epidermal growth factor receptor 3 (HER3) was screened and affinity was determined by enzyme-linked immunosorbent assay. Specificity was tested in MCF-7HER3-high, BT474HER3-high, and 293THER3-negative cells using flow cytometry and confocal microscopy. We further developed a HER3 aptamer-functionalized liposome encapsulating DOX and the efficiency of this ApDC was detected by cellular uptake analysis and cell viability assay. In MCF-7 tumor-bearing mice, tumor targeting evaluation, efficacy, toxicity and preliminary pharmocokinetic study was performed.Results: The candidate #13 aptamer had highest affinity (Kd =98±9.7 nM) and specificity. ApDC effectively reduces the half maximal inhibitory concentration of DOX compared with lipsome-DOX and free DOX. In vivo imaging and preliminary distribution studies showed that actively targeted nanoparticles, such as Apt-Lip-DOX molecules, could facilitate the delivery of DOX into tumors in MCF-7–bearing mice. This targeted chemotherapy caused greater tumor suppression than other groups and alleviated side effects such as weight loss, low survival rate, and organ (heart and liver) injury demonstrated by H&E staining.Conclusion: The results indicate that targeted chemotherapy using the aptamer–drug conjugate format could provide better tolerability and efficacy compared with non-targeted delivery in relatively low-dose toxic drugs. Keywords: breast cancer, human epidermal growth factor receptor 3, aptamer–drug conjugate, doxorubicin, cardiac toxicity, targeted therapyDou XQWang HZhang JWang FXu GLXu CCXu HHXiang SSFu JSong HFDove Medical PressarticleBreast cancerhuman epidermal growth factor receptor 3aptamer-drug conjugatedoxorubicincardiac toxicitytargeted therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 763-776 (2018)
institution DOAJ
collection DOAJ
language EN
topic Breast cancer
human epidermal growth factor receptor 3
aptamer-drug conjugate
doxorubicin
cardiac toxicity
targeted therapy
Medicine (General)
R5-920
spellingShingle Breast cancer
human epidermal growth factor receptor 3
aptamer-drug conjugate
doxorubicin
cardiac toxicity
targeted therapy
Medicine (General)
R5-920
Dou XQ
Wang H
Zhang J
Wang F
Xu GL
Xu CC
Xu HH
Xiang SS
Fu J
Song HF
Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity
description Xiao-qian Dou,1 Hua Wang,2 Jing Zhang,3 Fang Wang,3 Gui-li Xu,1 Cheng-cheng Xu,1 Huan-hua Xu,1 Shen-si Xiang,1 Jie Fu,1 Hai-feng Song1  1Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China; 2Ophthalmology Department, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China; 3Bioanalysis Department, United-Power Pharma Tech Co., Ltd., Beijing, China Introduction: The toxic side effects of doxorubicin (DOX) have limited its use in chemotherapy. Neither liposomal DOX nor pegylated liposomal DOX are able to completely resolve this issue. This is a proof-of-concept study testing aptamer-drug conjugate (ApDC) targeted delivery systems for chemotherapeutic drugs.Methods: Aptamer library targeting human epidermal growth factor receptor 3 (HER3) was screened and affinity was determined by enzyme-linked immunosorbent assay. Specificity was tested in MCF-7HER3-high, BT474HER3-high, and 293THER3-negative cells using flow cytometry and confocal microscopy. We further developed a HER3 aptamer-functionalized liposome encapsulating DOX and the efficiency of this ApDC was detected by cellular uptake analysis and cell viability assay. In MCF-7 tumor-bearing mice, tumor targeting evaluation, efficacy, toxicity and preliminary pharmocokinetic study was performed.Results: The candidate #13 aptamer had highest affinity (Kd =98±9.7 nM) and specificity. ApDC effectively reduces the half maximal inhibitory concentration of DOX compared with lipsome-DOX and free DOX. In vivo imaging and preliminary distribution studies showed that actively targeted nanoparticles, such as Apt-Lip-DOX molecules, could facilitate the delivery of DOX into tumors in MCF-7–bearing mice. This targeted chemotherapy caused greater tumor suppression than other groups and alleviated side effects such as weight loss, low survival rate, and organ (heart and liver) injury demonstrated by H&E staining.Conclusion: The results indicate that targeted chemotherapy using the aptamer–drug conjugate format could provide better tolerability and efficacy compared with non-targeted delivery in relatively low-dose toxic drugs. Keywords: breast cancer, human epidermal growth factor receptor 3, aptamer–drug conjugate, doxorubicin, cardiac toxicity, targeted therapy
format article
author Dou XQ
Wang H
Zhang J
Wang F
Xu GL
Xu CC
Xu HH
Xiang SS
Fu J
Song HF
author_facet Dou XQ
Wang H
Zhang J
Wang F
Xu GL
Xu CC
Xu HH
Xiang SS
Fu J
Song HF
author_sort Dou XQ
title Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity
title_short Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity
title_full Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity
title_fullStr Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity
title_full_unstemmed Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity
title_sort aptamer–drug conjugate: targeted delivery of doxorubicin in a her3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/d97216c704854400aacb4cc46a28b3e5
work_keys_str_mv AT douxq aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT wangh aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT zhangj aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT wangf aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT xugl aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT xucc aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT xuhh aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT xiangss aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT fuj aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
AT songhf aptamerndashdrugconjugatetargeteddeliveryofdoxorubicininaher3aptamerfunctionalizedliposomaldeliverysystemreducescardiotoxicity
_version_ 1718402739560513536

Ejemplares similares