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Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy
A new concept in cooperative adenine–uracil (A–U) hydrogen bonding interactions between anticancer drugs and nanocarrier complexes was successfully demonstrated by invoking the co-assembly of water soluble, uracil end-capped polyethylene glycol polymer (BU-PEG) upon association with the hydrophobic...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625492/ https://www.ncbi.nlm.nih.gov/pubmed/34834344 http://dx.doi.org/10.3390/pharmaceutics13111929 |
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author | Ilhami, Fasih Bintang Bayle, Enyew Alemayehu Cheng, Chih-Chia |
author_facet | Ilhami, Fasih Bintang Bayle, Enyew Alemayehu Cheng, Chih-Chia |
author_sort | Ilhami, Fasih Bintang |
collection | PubMed |
description | A new concept in cooperative adenine–uracil (A–U) hydrogen bonding interactions between anticancer drugs and nanocarrier complexes was successfully demonstrated by invoking the co-assembly of water soluble, uracil end-capped polyethylene glycol polymer (BU-PEG) upon association with the hydrophobic drug adenine-modified rhodamine (A-R6G). This concept holds promise as a smart and versatile drug delivery system for the achievement of targeted, more efficient cancer chemotherapy. Due to A–U base pairing between BU-PEG and A-R6G, BU-PEG has high tendency to interact with A-R6G, which leads to the formation of self-assembled A-R6G/BU-PEG nanogels in aqueous solution. The resulting nanogels exhibit a number of unique physical properties, including extremely high A-R6G-loading capacity, well-controlled, pH-triggered A-R6G release behavior, and excellent structural stability in biological media. Importantly, a series of in vitro cellular experiments clearly demonstrated that A-R6G/BU-PEG nanogels improved the selective uptake of A-R6G by cancer cells via endocytosis and promoted the intracellular release of A-R6G to subsequently induce apoptotic cell death, while control rhodamine/BU-PEG nanogels did not exert selective toxicity in cancer or normal cell lines. Overall, these results indicate that cooperative A–U base pairing within nanogels is a critical factor that improves selective drug uptake and effectively promotes apoptotic programmed cell death in cancer cells. |
format | Online Article Text |
id | pubmed-8625492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86254922021-11-27 Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy Ilhami, Fasih Bintang Bayle, Enyew Alemayehu Cheng, Chih-Chia Pharmaceutics Article A new concept in cooperative adenine–uracil (A–U) hydrogen bonding interactions between anticancer drugs and nanocarrier complexes was successfully demonstrated by invoking the co-assembly of water soluble, uracil end-capped polyethylene glycol polymer (BU-PEG) upon association with the hydrophobic drug adenine-modified rhodamine (A-R6G). This concept holds promise as a smart and versatile drug delivery system for the achievement of targeted, more efficient cancer chemotherapy. Due to A–U base pairing between BU-PEG and A-R6G, BU-PEG has high tendency to interact with A-R6G, which leads to the formation of self-assembled A-R6G/BU-PEG nanogels in aqueous solution. The resulting nanogels exhibit a number of unique physical properties, including extremely high A-R6G-loading capacity, well-controlled, pH-triggered A-R6G release behavior, and excellent structural stability in biological media. Importantly, a series of in vitro cellular experiments clearly demonstrated that A-R6G/BU-PEG nanogels improved the selective uptake of A-R6G by cancer cells via endocytosis and promoted the intracellular release of A-R6G to subsequently induce apoptotic cell death, while control rhodamine/BU-PEG nanogels did not exert selective toxicity in cancer or normal cell lines. Overall, these results indicate that cooperative A–U base pairing within nanogels is a critical factor that improves selective drug uptake and effectively promotes apoptotic programmed cell death in cancer cells. MDPI 2021-11-15 /pmc/articles/PMC8625492/ /pubmed/34834344 http://dx.doi.org/10.3390/pharmaceutics13111929 Text en © 2021 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 Ilhami, Fasih Bintang Bayle, Enyew Alemayehu Cheng, Chih-Chia Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy |
title | Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy |
title_full | Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy |
title_fullStr | Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy |
title_full_unstemmed | Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy |
title_short | Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy |
title_sort | complementary nucleobase interactions drive co-assembly of drugs and nanocarriers for selective cancer chemotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625492/ https://www.ncbi.nlm.nih.gov/pubmed/34834344 http://dx.doi.org/10.3390/pharmaceutics13111929 |
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