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...

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Autores principales:	Fasih Bintang Ilhami, Enyew Alemayehu Bayle, Chih-Chia Cheng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adenine–uracil base pair complementary hydrogen bonded drug carrier system controlled drug delivery supramolecular nanogels selective cytotoxicity Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/c0bf6f91d9f1485788db78533f58f76e
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spelling	oai:doaj.org-article:c0bf6f91d9f1485788db78533f58f76e2021-11-25T18:41:59ZComplementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy10.3390/pharmaceutics131119291999-4923https://doaj.org/article/c0bf6f91d9f1485788db78533f58f76e2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1929https://doaj.org/toc/1999-4923A 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.Fasih Bintang IlhamiEnyew Alemayehu BayleChih-Chia ChengMDPI AGarticleadenine–uracil base paircomplementary hydrogen bonded drug carrier systemcontrolled drug deliverysupramolecular nanogelsselective cytotoxicityPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1929, p 1929 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adenine–uracil base pair complementary hydrogen bonded drug carrier system controlled drug delivery supramolecular nanogels selective cytotoxicity Pharmacy and materia medica RS1-441
spellingShingle	adenine–uracil base pair complementary hydrogen bonded drug carrier system controlled drug delivery supramolecular nanogels selective cytotoxicity Pharmacy and materia medica RS1-441 Fasih Bintang Ilhami Enyew Alemayehu Bayle Chih-Chia Cheng Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy
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	article
author	Fasih Bintang Ilhami Enyew Alemayehu Bayle Chih-Chia Cheng
author_facet	Fasih Bintang Ilhami Enyew Alemayehu Bayle Chih-Chia Cheng
author_sort	Fasih Bintang Ilhami
title	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_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_sort	complementary nucleobase interactions drive co-assembly of drugs and nanocarriers for selective cancer chemotherapy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c0bf6f91d9f1485788db78533f58f76e
work_keys_str_mv	AT fasihbintangilhami complementarynucleobaseinteractionsdrivecoassemblyofdrugsandnanocarriersforselectivecancerchemotherapy AT enyewalemayehubayle complementarynucleobaseinteractionsdrivecoassemblyofdrugsandnanocarriersforselectivecancerchemotherapy AT chihchiacheng complementarynucleobaseinteractionsdrivecoassemblyofdrugsandnanocarriersforselectivecancerchemotherapy
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Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy

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