Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR

Oleic acid (OA) as main component of plant oil is an important solvent but seldom used in the nanocarrier of anticancer drugs because of strong hydrophobicity and little drug release. In order to develop a new type of OA nanomaterial with dual responses to pH and near infrared light (NIR) to achieve...

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Main Authors: Jin Zhang, Xiaoyue Tang, Chuanqing Huang, Zeyu Liu, Yong Ye
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/12/7/680
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author Jin Zhang
Xiaoyue Tang
Chuanqing Huang
Zeyu Liu
Yong Ye
author_facet Jin Zhang
Xiaoyue Tang
Chuanqing Huang
Zeyu Liu
Yong Ye
author_sort Jin Zhang
collection DOAJ
description Oleic acid (OA) as main component of plant oil is an important solvent but seldom used in the nanocarrier of anticancer drugs because of strong hydrophobicity and little drug release. In order to develop a new type of OA nanomaterial with dual responses to pH and near infrared light (NIR) to achieve the intelligent delivery of anticancer drugs. The novel OA copolymer (mPEG-PEI-(NBS, OA)) was synthesized by grafting OA and <i>o</i>-nitrobenzyl succinate (NBS) onto mPEGylated polyethyleneimine (mPEG-PEI) by amidation reaction. It was further conjugated with NaYF<sub>4</sub>:Yb<sup>3+</sup>/Er<sup>3+</sup> nanoparticles, and encapsulated doxorubicin (DOX) through self-assembly to make upconversion nanomicelles with dual response to pH and NIR. Drug release behavior of DOX, physicochemical characteristics of the nanomicelles were evaluated, along with its cytotoxic profile, as well as the degree of cellular uptake in A549 cells. The encapsulation efficiency and drug loading capacity of DOX in the nanomicelles were 73.84% ± 0.58% and 4.62% ± 0.28%, respectively, and the encapsulated DOX was quickly released in an acidic environment exposed to irradiation at 980 nm. The blank nanomicelles exhibited low cytotoxicity and excellent biocompatibility by MTT assay against A549 cells. The DOX-loaded nanomicelles showed remarkable cytotoxicity to A549 cells under NIR, and promoted the cellular uptake of DOX into the cytoplasm and nucleus of cancer cells. OA copolymer can effectively deliver DOX to cancer cells and achieve tumor targeting through a dual response to pH and NIR.
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spelling doaj.art-eb49c58315af40f1b8cb69203f5df4ed2023-11-20T07:16:56ZengMDPI AGPharmaceutics1999-49232020-07-0112768010.3390/pharmaceutics12070680Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIRJin Zhang0Xiaoyue Tang1Chuanqing Huang2Zeyu Liu3Yong Ye4Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, ChinaDepartment of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, ChinaDepartment of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, ChinaDepartment of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, ChinaDepartment of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, ChinaOleic acid (OA) as main component of plant oil is an important solvent but seldom used in the nanocarrier of anticancer drugs because of strong hydrophobicity and little drug release. In order to develop a new type of OA nanomaterial with dual responses to pH and near infrared light (NIR) to achieve the intelligent delivery of anticancer drugs. The novel OA copolymer (mPEG-PEI-(NBS, OA)) was synthesized by grafting OA and <i>o</i>-nitrobenzyl succinate (NBS) onto mPEGylated polyethyleneimine (mPEG-PEI) by amidation reaction. It was further conjugated with NaYF<sub>4</sub>:Yb<sup>3+</sup>/Er<sup>3+</sup> nanoparticles, and encapsulated doxorubicin (DOX) through self-assembly to make upconversion nanomicelles with dual response to pH and NIR. Drug release behavior of DOX, physicochemical characteristics of the nanomicelles were evaluated, along with its cytotoxic profile, as well as the degree of cellular uptake in A549 cells. The encapsulation efficiency and drug loading capacity of DOX in the nanomicelles were 73.84% ± 0.58% and 4.62% ± 0.28%, respectively, and the encapsulated DOX was quickly released in an acidic environment exposed to irradiation at 980 nm. The blank nanomicelles exhibited low cytotoxicity and excellent biocompatibility by MTT assay against A549 cells. The DOX-loaded nanomicelles showed remarkable cytotoxicity to A549 cells under NIR, and promoted the cellular uptake of DOX into the cytoplasm and nucleus of cancer cells. OA copolymer can effectively deliver DOX to cancer cells and achieve tumor targeting through a dual response to pH and NIR.https://www.mdpi.com/1999-4923/12/7/680oleic acid copolymerupconversion nanomaterialnanomicellesdrug deliverydual responsiveness
spellingShingle Jin Zhang
Xiaoyue Tang
Chuanqing Huang
Zeyu Liu
Yong Ye
Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR
Pharmaceutics
oleic acid copolymer
upconversion nanomaterial
nanomicelles
drug delivery
dual responsiveness
title Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR
title_full Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR
title_fullStr Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR
title_full_unstemmed Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR
title_short Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR
title_sort oleic acid copolymer as a novel upconversion nanomaterial to make doxorubicin loaded nanomicelles with dual responsiveness to ph and nir
topic oleic acid copolymer
upconversion nanomaterial
nanomicelles
drug delivery
dual responsiveness
url https://www.mdpi.com/1999-4923/12/7/680
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AT zeyuliu oleicacidcopolymerasanovelupconversionnanomaterialtomakedoxorubicinloadednanomicelleswithdualresponsivenesstophandnir
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