Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity

Functionalized gold nanoparticles (AuNPs) have been successfully used in many fields as a result of having low cytotoxicity, good biocompatibility, excellent optical properties, and their ability to target cancer cells. Here, we synthesized AuNP carriers that were modified by hyaluronic acid (HA), p...

Full description

Bibliographic Details
Main Authors: Lin-Song Li, Bin Ren, Xiaojing Yang, Zhong-Chao Cai, Xue-Jie Zhao, Mei-Xia Zhao
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/14/2/101
_version_ 1797406163163152384
author Lin-Song Li
Bin Ren
Xiaojing Yang
Zhong-Chao Cai
Xue-Jie Zhao
Mei-Xia Zhao
author_facet Lin-Song Li
Bin Ren
Xiaojing Yang
Zhong-Chao Cai
Xue-Jie Zhao
Mei-Xia Zhao
author_sort Lin-Song Li
collection DOAJ
description Functionalized gold nanoparticles (AuNPs) have been successfully used in many fields as a result of having low cytotoxicity, good biocompatibility, excellent optical properties, and their ability to target cancer cells. Here, we synthesized AuNP carriers that were modified by hyaluronic acid (HA), polyethylene glycol (PEG), and adipic dihydrazide (ADH). The antitumor drug doxorubicin (Dox) was loaded into AuNP carriers and attached chemically. The Au nanocomposite AuNPs@MPA-PEG-HA-ADH-Dox was able to disperse uniformly in aqueous solution, with a diameter of 15 nm. The results of a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that AuNP carriers displayed very little toxicity toward cells in high doses, although the antitumor properties of Au nanocomposites were significantly enhanced. Cellular uptake experiments demonstrated that AuNPs modified with hyaluronic acid were more readily ingested by HepG2 and HCT-116 cells, as they have a large number of CD44 receptors. A series of experiments measuring apoptosis such as Rh123 and annexin V-FITC staining, and analysis of mitochondrial membrane potential (MMP) analysis, indicated that apoptosis played a role in the inhibition of cell proliferation by AuNPs@MPA-PEG-HA-ADH-Dox. Excessive production of reactive oxygen species (ROS) was the principal mechanism by which the Au nanocomposites inhibited cell proliferation, leading to apoptosis. Thus, the Au nanocomposites, which allowed cell imaging in real-time and induced apoptosis in specific cell types, represent theragnostic agents with potential for future clinical applications in bowel cancer.
first_indexed 2024-03-09T03:21:26Z
format Article
id doaj.art-549374d7b52347fcb9cfe64f7f650798
institution Directory Open Access Journal
issn 1424-8247
language English
last_indexed 2024-03-09T03:21:26Z
publishDate 2021-01-01
publisher MDPI AG
record_format Article
series Pharmaceuticals
spelling doaj.art-549374d7b52347fcb9cfe64f7f6507982023-12-03T15:08:50ZengMDPI AGPharmaceuticals1424-82472021-01-0114210110.3390/ph14020101Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their BioactivityLin-Song Li0Bin Ren1Xiaojing Yang2Zhong-Chao Cai3Xue-Jie Zhao4Mei-Xia Zhao5Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng 475004, ChinaSchool of Mathematics and Statistics, Henan University, Jinming Campus, Kaifeng 475004, ChinaKey Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng 475004, ChinaKey Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng 475004, ChinaKey Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng 475004, ChinaKey Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng 475004, ChinaFunctionalized gold nanoparticles (AuNPs) have been successfully used in many fields as a result of having low cytotoxicity, good biocompatibility, excellent optical properties, and their ability to target cancer cells. Here, we synthesized AuNP carriers that were modified by hyaluronic acid (HA), polyethylene glycol (PEG), and adipic dihydrazide (ADH). The antitumor drug doxorubicin (Dox) was loaded into AuNP carriers and attached chemically. The Au nanocomposite AuNPs@MPA-PEG-HA-ADH-Dox was able to disperse uniformly in aqueous solution, with a diameter of 15 nm. The results of a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that AuNP carriers displayed very little toxicity toward cells in high doses, although the antitumor properties of Au nanocomposites were significantly enhanced. Cellular uptake experiments demonstrated that AuNPs modified with hyaluronic acid were more readily ingested by HepG2 and HCT-116 cells, as they have a large number of CD44 receptors. A series of experiments measuring apoptosis such as Rh123 and annexin V-FITC staining, and analysis of mitochondrial membrane potential (MMP) analysis, indicated that apoptosis played a role in the inhibition of cell proliferation by AuNPs@MPA-PEG-HA-ADH-Dox. Excessive production of reactive oxygen species (ROS) was the principal mechanism by which the Au nanocomposites inhibited cell proliferation, leading to apoptosis. Thus, the Au nanocomposites, which allowed cell imaging in real-time and induced apoptosis in specific cell types, represent theragnostic agents with potential for future clinical applications in bowel cancer.https://www.mdpi.com/1424-8247/14/2/101hyaluronic acidgold nanoparticlesdrug carrierstheragnostic agentsimaging
spellingShingle Lin-Song Li
Bin Ren
Xiaojing Yang
Zhong-Chao Cai
Xue-Jie Zhao
Mei-Xia Zhao
Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity
Pharmaceuticals
hyaluronic acid
gold nanoparticles
drug carriers
theragnostic agents
imaging
title Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity
title_full Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity
title_fullStr Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity
title_full_unstemmed Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity
title_short Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity
title_sort hyaluronic acid modified and doxorubicin loaded gold nanoparticles and evaluation of their bioactivity
topic hyaluronic acid
gold nanoparticles
drug carriers
theragnostic agents
imaging
url https://www.mdpi.com/1424-8247/14/2/101
work_keys_str_mv AT linsongli hyaluronicacidmodifiedanddoxorubicinloadedgoldnanoparticlesandevaluationoftheirbioactivity
AT binren hyaluronicacidmodifiedanddoxorubicinloadedgoldnanoparticlesandevaluationoftheirbioactivity
AT xiaojingyang hyaluronicacidmodifiedanddoxorubicinloadedgoldnanoparticlesandevaluationoftheirbioactivity
AT zhongchaocai hyaluronicacidmodifiedanddoxorubicinloadedgoldnanoparticlesandevaluationoftheirbioactivity
AT xuejiezhao hyaluronicacidmodifiedanddoxorubicinloadedgoldnanoparticlesandevaluationoftheirbioactivity
AT meixiazhao hyaluronicacidmodifiedanddoxorubicinloadedgoldnanoparticlesandevaluationoftheirbioactivity