The University of Southampton
University of Southampton Institutional Repository

Zwitterionic targeting Doxorubicin - loaded micelles assembled by amphiphilic dendrimers with enhanced antitumor performance

Zwitterionic targeting Doxorubicin - loaded micelles assembled by amphiphilic dendrimers with enhanced antitumor performance
Zwitterionic targeting Doxorubicin - loaded micelles assembled by amphiphilic dendrimers with enhanced antitumor performance

Chemotherapy is the main method of treating malignant tumors in clinical treatment. However, the commonly used chemotherapeutic drugs have the disadvantages of high biological toxicity, poor water solubility, low targeting ability, and high side effects. Zwitterionic micelles assembled by amphiphilic dendrimers modified with zwitterionic groups and targeting ligand should largely overcome these shortcomings. Herein, the zwitterionic group and targeting peptide c(RGDfC) were modified on the surface of generation 2 poly(propylene imine) dendrimers (G2 PPI), which was conjugated with hydrophobic N-(2-mercaptoethyl) oleamide to form amphiphilic dendrimers (PPIMYRC). PPIMYRC self-assembled into micelles with doxorubicin (DOX) loaded in the interior of micelles to prepare DOX-loaded micelles (PPIMYRC-DOX micelles). The PPIMYRC-DOX micelles had great stability in fibrinogen and pH-responsive drug release. Furthermore, PPIMYRC-DOX micelles had higher cellular uptake rates than free DOX, resulting in higher cytotoxicity of PPIMYRC-DOX micelles than that of free DOX. More importantly, PPIMYRC-DOX micelles inhibited tumors much better than free DOX. The tumor inhibition rate of PPIMYRC-DOX micelles was as high as 93%. Taken together, PPIMYRC-DOX micelles were assembled by amphiphilic dendrimers with the zwitterionic and targeting groups, which enhanced the therapeutic effect of DOX and reduced its side effects. The prepared targeting nanodrug has great potential for further application in antitumor therapy.

0743-7463
4766-4776
Zhang, Lu
93bf816a-d13b-4f19-a513-e6f23b3be8aa
Guo, Quanling
576232b7-47af-4e7c-a971-c26584b16125
Zheng, Ruixue
a02fa853-83ff-4ea9-aceb-b2f7f22c15e9
Yu, Qingyu
fde488b8-fa02-463b-8cbd-a067928747b6
Liang, Ying
2fb56af7-bd8c-452c-94fd-e04fe98e61b6
Ma, Guanglong
4ba2ed72-fcf8-4116-8548-6d4774a80934
Li, Qiurong
0df42a3a-9baa-4e88-99dd-9af19f9539ba
Zhang, Xiaoyu
c3181da9-f55f-4fd3-a5c8-0fa12d339259
Xiao, Haiyan
d4f2d0c6-ad07-4630-871a-2b006e6e9e39
Wang, Longgang
fa6e2c69-1986-4161-b285-774fb453e124
Zhang, Lu
93bf816a-d13b-4f19-a513-e6f23b3be8aa
Guo, Quanling
576232b7-47af-4e7c-a971-c26584b16125
Zheng, Ruixue
a02fa853-83ff-4ea9-aceb-b2f7f22c15e9
Yu, Qingyu
fde488b8-fa02-463b-8cbd-a067928747b6
Liang, Ying
2fb56af7-bd8c-452c-94fd-e04fe98e61b6
Ma, Guanglong
4ba2ed72-fcf8-4116-8548-6d4774a80934
Li, Qiurong
0df42a3a-9baa-4e88-99dd-9af19f9539ba
Zhang, Xiaoyu
c3181da9-f55f-4fd3-a5c8-0fa12d339259
Xiao, Haiyan
d4f2d0c6-ad07-4630-871a-2b006e6e9e39
Wang, Longgang
fa6e2c69-1986-4161-b285-774fb453e124

Zhang, Lu, Guo, Quanling, Zheng, Ruixue, Yu, Qingyu, Liang, Ying, Ma, Guanglong, Li, Qiurong, Zhang, Xiaoyu, Xiao, Haiyan and Wang, Longgang (2023) Zwitterionic targeting Doxorubicin - loaded micelles assembled by amphiphilic dendrimers with enhanced antitumor performance. Langmuir, 39 (13), 4766-4776. (doi:10.1021/acs.langmuir.3c00159).

Record type: Article

Abstract

Chemotherapy is the main method of treating malignant tumors in clinical treatment. However, the commonly used chemotherapeutic drugs have the disadvantages of high biological toxicity, poor water solubility, low targeting ability, and high side effects. Zwitterionic micelles assembled by amphiphilic dendrimers modified with zwitterionic groups and targeting ligand should largely overcome these shortcomings. Herein, the zwitterionic group and targeting peptide c(RGDfC) were modified on the surface of generation 2 poly(propylene imine) dendrimers (G2 PPI), which was conjugated with hydrophobic N-(2-mercaptoethyl) oleamide to form amphiphilic dendrimers (PPIMYRC). PPIMYRC self-assembled into micelles with doxorubicin (DOX) loaded in the interior of micelles to prepare DOX-loaded micelles (PPIMYRC-DOX micelles). The PPIMYRC-DOX micelles had great stability in fibrinogen and pH-responsive drug release. Furthermore, PPIMYRC-DOX micelles had higher cellular uptake rates than free DOX, resulting in higher cytotoxicity of PPIMYRC-DOX micelles than that of free DOX. More importantly, PPIMYRC-DOX micelles inhibited tumors much better than free DOX. The tumor inhibition rate of PPIMYRC-DOX micelles was as high as 93%. Taken together, PPIMYRC-DOX micelles were assembled by amphiphilic dendrimers with the zwitterionic and targeting groups, which enhanced the therapeutic effect of DOX and reduced its side effects. The prepared targeting nanodrug has great potential for further application in antitumor therapy.

Text
Zwitterionic targeting doxorubicin - Accepted Manuscript
Download (4MB)

More information

Accepted/In Press date: 8 March 2023
Published date: 20 March 2023
Additional Information: Funding Information: This research was funded by the Natural Science Foundation of Hebei Province (B2017203229, H2022203004), Subsidy for Hebei Key Laboratory of Applied Chemistry after Operation Performance (22567616H) and Yanshan University's Specialty (Medical Engineering Interdisciplinarity) Cultivation Project (UH202209). Publisher Copyright: © 2023 American Chemical Society.

Identifiers

Local EPrints ID: 477601
URI: http://eprints.soton.ac.uk/id/eprint/477601
ISSN: 0743-7463
PURE UUID: f4513122-f162-4ba7-928f-5c0e50aa1de7

Catalogue record

Date deposited: 09 Jun 2023 16:33
Last modified: 06 Jun 2024 04:14

Export record

Altmetrics

Contributors

Author: Lu Zhang
Author: Quanling Guo
Author: Ruixue Zheng
Author: Qingyu Yu
Author: Ying Liang
Author: Guanglong Ma
Author: Qiurong Li
Author: Xiaoyu Zhang
Author: Haiyan Xiao
Author: Longgang Wang

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×