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Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin

As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released D...

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Autores principales: Song, Xinyue, Yan, Tao, Tian, Feng, Li, Fengyan, Ren, Linlin, Li, Qiong, Zhang, Shusheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937813/
https://www.ncbi.nlm.nih.gov/pubmed/33692990
http://dx.doi.org/10.3389/fbioe.2021.639487
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author Song, Xinyue
Yan, Tao
Tian, Feng
Li, Fengyan
Ren, Linlin
Li, Qiong
Zhang, Shusheng
author_facet Song, Xinyue
Yan, Tao
Tian, Feng
Li, Fengyan
Ren, Linlin
Li, Qiong
Zhang, Shusheng
author_sort Song, Xinyue
collection PubMed
description As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.
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spelling pubmed-79378132021-03-09 Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin Song, Xinyue Yan, Tao Tian, Feng Li, Fengyan Ren, Linlin Li, Qiong Zhang, Shusheng Front Bioeng Biotechnol Bioengineering and Biotechnology As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth. Frontiers Media S.A. 2021-02-22 /pmc/articles/PMC7937813/ /pubmed/33692990 http://dx.doi.org/10.3389/fbioe.2021.639487 Text en Copyright © 2021 Song, Yan, Tian, Li, Ren, Li and Zhang. http://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 Bioengineering and Biotechnology
Song, Xinyue
Yan, Tao
Tian, Feng
Li, Fengyan
Ren, Linlin
Li, Qiong
Zhang, Shusheng
Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin
title Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin
title_full Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin
title_fullStr Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin
title_full_unstemmed Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin
title_short Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin
title_sort aptamer functionalized upconversion nanotheranostic agent with nuclear targeting as the highly localized drug-delivery system of doxorubicin
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937813/
https://www.ncbi.nlm.nih.gov/pubmed/33692990
http://dx.doi.org/10.3389/fbioe.2021.639487
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