A transformable amphiphilic and block polymer-dendron conjugate for enhanced tumor penetration and retention with cellular homeostasis perturbation via membrane flow.
File(s)
Supporting information
Author(s)
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.
Date Issued
2022-04-21
Date Acceptance
2022-02-01
Citation
Advanced Materials, 2022, 34 (16), pp.1-14
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
Engineering and Physical Sciences Research Council
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35170102
Subjects
cancer cellular homeostasis
membrane flow
polymer-dendron conjugates
stealthy-to-sticky transition
stimuli-responsive drug delivery systems
tumor penetration and retention
Publication Status
Published
Coverage Spatial
Germany
Date Publish Online
2022-02-16