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A transformable amphiphilic and block polymer-dendron conjugate for enhanced tumor penetration and retention with cellular homeostasis perturbation via membrane flow.

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Gu et al., Advanced Materials 2022_Accepted Manuscript.pdfFile embargoed until 15 February 20231.06 MBAdobe PDF    Request a copy
Gu et al., Advanced Materials 2022, Supporting Information.pdfFile embargoed until 15 February 202314.48 MBAdobe PDF    Request a copy
Title: A transformable amphiphilic and block polymer-dendron conjugate for enhanced tumor penetration and retention with cellular homeostasis perturbation via membrane flow.
Authors: Gu, L
Duan, Z
Chen, X
Li, X
Luo, Q
Bhamra, A
Pan, D
Zhu, H
Tian, X
Chen, R
Gu, Z
Zhang, H
Qian, Z
Gong, Q
Luo, K
Item Type: Journal Article
Abstract: Efficient penetration and retention of therapeutic agents in tumor tissues can be realized through rational design of drug delivery systems. Herein, we present a polymer-dendron conjugate, POEGMA-b-p(GFLG-Dendron-Ppa) (GFLG-DP), which allows cathepsin B (CTSB)-triggered stealthy-to-sticky structural transformation. The compositions and ratios were optimized through dissipative particle dynamics simulations. GFLG-DP displayed tumor-specific transformation and consequently released dendron-Ppa was found to effectively accumulate on the tumor cell membrane. The interaction between dendron-Ppa and the tumor cell membrane resulted in intracellular and intercellular transport via membrane flow, thus achieving efficient deep penetration and prolonged retention of therapeutic agents in solid tumor tissues. Meanwhile, the interaction of dendron-Ppa with endoplasmic reticulum disrupted the cell homeostasis, making tumor cells more vulnerable and susceptible to the photodynamic therapy. This platform represents a versatile approach to augmenting the tumor therapeutic efficacy of a nanomedicine via manipulation of its interactions with tumor membrane systems. This article is protected by copyright. All rights reserved.
Issue Date: 21-Apr-2022
Date of Acceptance: 1-Feb-2022
URI: http://hdl.handle.net/10044/1/94980
DOI: 10.1002/adma.202200048
ISSN: 0935-9648
Publisher: Wiley
Start Page: 1
End Page: 14
Journal / Book Title: Advanced Materials
Volume: 34
Issue: 16
Copyright Statement: This article is protected by copyright. All rights reserved
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
cancer cellular homeostasis
membrane flow
polymer-dendron conjugates
stealthy-to-sticky transition
stimuli-responsive drug delivery systems
tumor penetration and retention
CATHEPSIN-B
CANCER
MACROPINOCYTOSIS
MICROENVIRONMENT
MECHANISMS
DEATH
CELLS
cancer cellular homeostasis
membrane flow
polymer−dendron conjugates
stealthy-to-sticky transition
stimuli-responsive drug delivery systems
tumor penetration and retention
Anthracenes
Cell Line, Tumor
Dendrimers
Homeostasis
Humans
Nanoparticles
Neoplasms
Polymers
Cell Line, Tumor
Humans
Neoplasms
Anthracenes
Polymers
Homeostasis
Dendrimers
Nanoparticles
cancer cellular homeostasis
membrane flow
polymer-dendron conjugates
stealthy-to-sticky transition
stimuli-responsive drug delivery systems
tumor penetration and retention
Nanoscience & Nanotechnology
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Publication Status: Published
Conference Place: Germany
Embargo Date: 2023-02-15
Online Publication Date: 2022-02-16
Appears in Collections:Chemical Engineering
Faculty of Engineering