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A dendritic polymer-based nanosystem mediates drug penetration and irreversible endoplasmic reticulum stresses in tumor via neighboring effect.

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Zheng et al., Advanced Materials 2022_Accpeted Manuscript.pdfFile embargoed until 14 March 20232.59 MBAdobe PDF    Request a copy
Zheng et al., Advanced Materials 2022_Supporting Information.pdfFile embargoed until 14 March 202320.43 MBAdobe PDF    Request a copy
Title: A dendritic polymer-based nanosystem mediates drug penetration and irreversible endoplasmic reticulum stresses in tumor via neighboring effect.
Authors: Zheng, X
Pan, D
Zhu, G
Zhang, L
Bhamra, A
Chen, R
Zhang, H
Gong, Q
Gu, Z
Luo, K
Item Type: Journal Article
Abstract: Nanoparticles (NPs)-based cancer therapeutics is generally impeded by poor drug penetration into solid tumors due to their dense tumor extracellular matrix (ECM). Herein, we develop pH/redox-responsive dendritic polymer-based NPs to amplify the neighboring effect for improving drug penetration and driving cell apoptosis via combination therapy. Pyropheophorbide a (Ppa) is conjugated with PEGylated dendritic peptides via disulfide bonds and doxorubicin (DOX) encapsulated in the conjugate to construct dual-responsive NPs, PDPP@D. Delayed released DOX and Ppa from PDPP@D exert their combination therapeutic effect to induce cell apoptosis, and then they are liberated out of dying cells to amplify the neighboring effect, resulting in their diffusion through the dense ECM and penetration into solid tumors. Transcriptome studies reveal that PDPP@D leads to irreversible stress on the endoplasmic reticulum and inhibits cell protection through blocking the IRE1-dependent survival pathway and unleashing the DR5-mediated caspase activity to promote cell death. The strategy of amplifying the neighboring effect of NPs through combination therapy may offer great potential in enhancing drug penetration and eradicating solid tumors. This article is protected by copyright. All rights reserved.
Issue Date: 15-Mar-2022
Date of Acceptance: 15-Mar-2022
URI: http://hdl.handle.net/10044/1/96012
DOI: 10.1002/adma.202201200
ISSN: 0935-9648
Publisher: Wiley
Start Page: 1
End Page: 14
Journal / Book Title: Advanced Materials
Volume: 34
Issue: 20
Copyright Statement: © 2022 John Wiley & Sons Ltd. This is the pre-peer reviewed version of the following article: , Zheng, X., Pan, D., Zhu, G., Zhang, L., Bhamra, A., Chen, R., Zhang, H., Gong, Q., Gu, Z. and Luo, K. (2022), A dendritic polymer-based nanosystem mediates drug penetration and irreversible endoplasmic reticulum stresses in tumor via neighboring effect. Adv. Mater.. Accepted Author Manuscript 2201200. https://doi.org/10.1002/adma.202201200
Sponsor/Funder: Engineering and Physical Sciences Research Council
Keywords: Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Chemistry, Physical
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Physics, Applied
Physics, Condensed Matter
Chemistry
Science & Technology - Other Topics
Materials Science
Physics
combination therapy
drug delivery
drug penetration
endoplasmic reticulum stresses
neighboring effect
NANOPARTICLES
combination therapy
drug delivery
drug penetration
endoplasmic reticulum stresses
neighboring effect
combination therapy
drug delivery
drug penetration
endoplasmic reticulum stresses
neighboring effect
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Nanoscience & Nanotechnology
Publication Status: Published
Conference Place: Germany
Embargo Date: 2023-03-14
Online Publication Date: 2022-03-15
Appears in Collections:Chemical Engineering
Faculty of Engineering