Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast Cancer
Kamel S Ahmed,1,2,* Shenhuan Liu,1,* Jing Mao,1 Jie Zhang,3 Lipeng Qiu1 1School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, Jiangsu, People’s Republic of China; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 19623, Egypt; 3The Jiaxing K...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-07-01
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| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/dual-functional-peptide-driven-liposome-codelivery-system-for-efficien-peer-reviewed-fulltext-article-DDDT |
| _version_ | 1818652183514578944 |
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| author | Ahmed KS Liu S Mao J Zhang J Qiu L |
| author_facet | Ahmed KS Liu S Mao J Zhang J Qiu L |
| author_sort | Ahmed KS |
| collection | DOAJ |
| description | Kamel S Ahmed,1,2,* Shenhuan Liu,1,* Jing Mao,1 Jie Zhang,3 Lipeng Qiu1 1School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, Jiangsu, People’s Republic of China; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 19623, Egypt; 3The Jiaxing Key Laboratory of Oncological Photodynamic Therapy and the Targeted Drug Research, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, 314001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Zhang; Lipeng Qiu Email zhangjiepharm@zjxu.edu.cn; flyqlp@163.comBackground: The active-targeted drug delivery systems had attracted more and more attention to efficiently overcome multidrug resistance (MDR) in cancer treatments. The aim of the work was to develop a multifunctional nano-structured liposomal system for co-delivery of doxorubicin hydrochloride (DOX) and celecoxib (CEL) to overcome doxorubicin resistance in breast cancer.Methods: A functional hybrid peptide (MTS-R8H3) with unique cellular penetrability, endo-lysosomal escape and mitochondrial targeting ability was successfully synthesized using solid phase synthesis technology. The peptide modified targeted liposomes (DOX/CEL-MTS-R8H3 lipo) for co-delivery of DOX and CEL were formulated to overcome the chemoresistance in MCF/ADR cells.Results: DOX/CEL-MTS-R8H3 lipo showed nanosized shape and displayed high stability for one month. The cytotoxicity effect of the co-delivery of DOX and CEL through peptide modified liposomes had remarkable treatment efficacy on killing MCF/ADR cells. Targeted liposome exhibited greater cellular entry ability about 5.72-fold stronger than DOX solution. Moreover, as compared with unmodified liposomes, the presence of MTS-R8H3 peptide entity on liposome surface enhanced the mitochondrial-targeting ability and achieved effective reactive oxygen species (ROS) production with significant inhibition of P-gp efflux activity.Conclusion: The study suggested that the DOX/CEL-MTS-R8H3 lipo is a promising strategy for overcoming drug resistance in breast cancer treatments with high targeting inhibition efficiency.Keywords: doxorubicin hydrochloride, celecoxib, co-delivery, targeting liposomes, multidrug resistance |
| first_indexed | 2024-12-17T02:17:57Z |
| format | Article |
| id | doaj.art-22b6962fc50b40fd97031fdfbd84f68a |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-17T02:17:57Z |
| publishDate | 2021-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-22b6962fc50b40fd97031fdfbd84f68a2022-12-21T22:07:19ZengDove Medical PressDrug Design, Development and Therapy1177-88812021-07-01Volume 153223323967341Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast CancerAhmed KSLiu SMao JZhang JQiu LKamel S Ahmed,1,2,* Shenhuan Liu,1,* Jing Mao,1 Jie Zhang,3 Lipeng Qiu1 1School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, Jiangsu, People’s Republic of China; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 19623, Egypt; 3The Jiaxing Key Laboratory of Oncological Photodynamic Therapy and the Targeted Drug Research, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, 314001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Zhang; Lipeng Qiu Email zhangjiepharm@zjxu.edu.cn; flyqlp@163.comBackground: The active-targeted drug delivery systems had attracted more and more attention to efficiently overcome multidrug resistance (MDR) in cancer treatments. The aim of the work was to develop a multifunctional nano-structured liposomal system for co-delivery of doxorubicin hydrochloride (DOX) and celecoxib (CEL) to overcome doxorubicin resistance in breast cancer.Methods: A functional hybrid peptide (MTS-R8H3) with unique cellular penetrability, endo-lysosomal escape and mitochondrial targeting ability was successfully synthesized using solid phase synthesis technology. The peptide modified targeted liposomes (DOX/CEL-MTS-R8H3 lipo) for co-delivery of DOX and CEL were formulated to overcome the chemoresistance in MCF/ADR cells.Results: DOX/CEL-MTS-R8H3 lipo showed nanosized shape and displayed high stability for one month. The cytotoxicity effect of the co-delivery of DOX and CEL through peptide modified liposomes had remarkable treatment efficacy on killing MCF/ADR cells. Targeted liposome exhibited greater cellular entry ability about 5.72-fold stronger than DOX solution. Moreover, as compared with unmodified liposomes, the presence of MTS-R8H3 peptide entity on liposome surface enhanced the mitochondrial-targeting ability and achieved effective reactive oxygen species (ROS) production with significant inhibition of P-gp efflux activity.Conclusion: The study suggested that the DOX/CEL-MTS-R8H3 lipo is a promising strategy for overcoming drug resistance in breast cancer treatments with high targeting inhibition efficiency.Keywords: doxorubicin hydrochloride, celecoxib, co-delivery, targeting liposomes, multidrug resistancehttps://www.dovepress.com/dual-functional-peptide-driven-liposome-codelivery-system-for-efficien-peer-reviewed-fulltext-article-DDDTdoxorubicin hydrochloridecelecoxibco-deliverytargeting liposomesmultidrug resistance |
| spellingShingle | Ahmed KS Liu S Mao J Zhang J Qiu L Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast Cancer Drug Design, Development and Therapy doxorubicin hydrochloride celecoxib co-delivery targeting liposomes multidrug resistance |
| title | Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast Cancer |
| title_full | Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast Cancer |
| title_fullStr | Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast Cancer |
| title_full_unstemmed | Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast Cancer |
| title_short | Dual-Functional Peptide Driven Liposome Codelivery System for Efficient Treatment of Doxorubicin-Resistant Breast Cancer |
| title_sort | dual functional peptide driven liposome codelivery system for efficient treatment of doxorubicin resistant breast cancer |
| topic | doxorubicin hydrochloride celecoxib co-delivery targeting liposomes multidrug resistance |
| url | https://www.dovepress.com/dual-functional-peptide-driven-liposome-codelivery-system-for-efficien-peer-reviewed-fulltext-article-DDDT |
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