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Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity

Cell surface thiols can be targeted by thiol-reactive groups of various materials such as peptides, nanoparticles, and polymers. Here, we used the maleimide group, which can rapidly and covalently conjugate with thiol groups, to prepare surface-modified liposomes (M-Lip) that prolong retention of do...

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Detalles Bibliográficos
Autores principales: Tang, Chuane, Yin, Dan, Liu, Tianya, Gou, Rui, Fu, Jiao, Tang, Qi, Wang, Yao, Zou, Liang, Li, Hanmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320254/
https://www.ncbi.nlm.nih.gov/pubmed/35889500
http://dx.doi.org/10.3390/molecules27144632
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author Tang, Chuane
Yin, Dan
Liu, Tianya
Gou, Rui
Fu, Jiao
Tang, Qi
Wang, Yao
Zou, Liang
Li, Hanmei
author_facet Tang, Chuane
Yin, Dan
Liu, Tianya
Gou, Rui
Fu, Jiao
Tang, Qi
Wang, Yao
Zou, Liang
Li, Hanmei
author_sort Tang, Chuane
collection PubMed
description Cell surface thiols can be targeted by thiol-reactive groups of various materials such as peptides, nanoparticles, and polymers. Here, we used the maleimide group, which can rapidly and covalently conjugate with thiol groups, to prepare surface-modified liposomes (M-Lip) that prolong retention of doxorubicin (Dox) at tumor sites, enhancing its efficacy. Surface modification with the maleimide moiety had no effect on the drug loading efficiency or drug release properties. Compared to unmodified Lip/Dox, M-Lip/Dox was retained longer at the tumor site, it was taken up by 4T1 cells to a significantly greater extent, and exhibited stronger inhibitory effect against 4T1 cells. The in vivo imaging results showed that the retention time of M-Lip at the tumor was significantly longer than that of Lip. In addition, M-Lip/Dox also showed significantly higher anticancer efficacy and lower cardiotoxicity than Lip/Dox in mice bearing 4T1 tumor xenografts. Thus, the modification strategy with maleimide may be useful for achieving higher efficient liposome for tumor therapy.
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spelling pubmed-93202542022-07-27 Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity Tang, Chuane Yin, Dan Liu, Tianya Gou, Rui Fu, Jiao Tang, Qi Wang, Yao Zou, Liang Li, Hanmei Molecules Article Cell surface thiols can be targeted by thiol-reactive groups of various materials such as peptides, nanoparticles, and polymers. Here, we used the maleimide group, which can rapidly and covalently conjugate with thiol groups, to prepare surface-modified liposomes (M-Lip) that prolong retention of doxorubicin (Dox) at tumor sites, enhancing its efficacy. Surface modification with the maleimide moiety had no effect on the drug loading efficiency or drug release properties. Compared to unmodified Lip/Dox, M-Lip/Dox was retained longer at the tumor site, it was taken up by 4T1 cells to a significantly greater extent, and exhibited stronger inhibitory effect against 4T1 cells. The in vivo imaging results showed that the retention time of M-Lip at the tumor was significantly longer than that of Lip. In addition, M-Lip/Dox also showed significantly higher anticancer efficacy and lower cardiotoxicity than Lip/Dox in mice bearing 4T1 tumor xenografts. Thus, the modification strategy with maleimide may be useful for achieving higher efficient liposome for tumor therapy. MDPI 2022-07-20 /pmc/articles/PMC9320254/ /pubmed/35889500 http://dx.doi.org/10.3390/molecules27144632 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tang, Chuane
Yin, Dan
Liu, Tianya
Gou, Rui
Fu, Jiao
Tang, Qi
Wang, Yao
Zou, Liang
Li, Hanmei
Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity
title Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity
title_full Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity
title_fullStr Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity
title_full_unstemmed Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity
title_short Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity
title_sort maleimide-functionalized liposomes: prolonged retention and enhanced efficacy of doxorubicin in breast cancer with low systemic toxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320254/
https://www.ncbi.nlm.nih.gov/pubmed/35889500
http://dx.doi.org/10.3390/molecules27144632
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