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Stimuli-sensitive linear-dendritic block copolymer-drug prodrug as nano-platform for tumor combination therapy.

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Cai et al., Advanced Materials 2021_Accepted Manuscript.pdfFile embargoed until 06 December 20226.53 MBAdobe PDF    Request a copy
Cai et al., Advanced Materials 2021_Supporting Information.pdfFile embargoed until 06 December 202222.43 MBAdobe PDF    Request a copy
Title: Stimuli-sensitive linear-dendritic block copolymer-drug prodrug as nano-platform for tumor combination therapy.
Authors: Cai, H
Tan, P
Chen, X
Kopytynski, M
Pan, D
Zheng, X
Gu, L
Gong, Q
Tian, X
Gu, Z
Zhang, H
Chen, R
Luo, K
Item Type: Journal Article
Abstract: Linear-dendritic block copolymer (LDBCs) are highly attractive candidates for smart drug delivery vehicles. Herein, we report an amphiphilic poly[(ethylene glycol) methyl ether methacrylate] (POEGMA) linear-peptide dendritic prodrug of doxorubicin (DOX) prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. A hydrophobic dye-based photosensitizer chlorin e6 (Ce6) was employed for encapsulation in the prodrug nanoparticles (NPs) to obtain a LDBCs-based drug delivery system (LD-DOX/Ce6) which offered a combination cancer therapy. Due to the presence of Gly-Phe-Leu-Gly peptides and hydrazone bonds in the prodrug structure, LD-DOX/Ce6 were degraded into small fragments, thus specifically triggering the intracellular release of DOX and Ce6 in the tumor microenvironment. Bioinformatics analysis suggested that LD-DOX/Ce6 with laser irradiation treatment significantly induced apoptosis, DNA damage and cell cycle arrest. The combination treatment could not only suppress tumor growth, but also significantly reduced tumor metastasis compared with treatments with DOX or Ce6 through regulating EMT pathway, TGFβ pathway, angiogenesis and the hypoxia pathway. LD-DOX/Ce6 displayed a synergistic chemo-photodynamic anti-tumor efficacy, resulting in a high inhibition in tumor growth and metastasis, while maintaining an excellent biosafety. Therefore, this study has demonstrated potential of the biodegradable and tumor microenvironment-responsive LDBCs as an intelligent multifunctional drug delivery vehicle for high-efficiency cancer combination therapy. This article is protected by copyright. All rights reserved.
Issue Date: 24-Feb-2022
Date of Acceptance: 6-Dec-2021
URI: http://hdl.handle.net/10044/1/93461
DOI: 10.1002/adma.202108049
ISSN: 0935-9648
Publisher: Wiley
Start Page: 1
End Page: 15
Journal / Book Title: Advanced Materials
Volume: 34
Issue: 8
Copyright Statement: © 2022 Wiley-VCH GmbH. All rights reserved. This is the accepted version of the following article: Cai, H., Tan, P., Chen, X., Kopytynski, M., Pan, D., Zheng, X., Gu, L., Gong, Q., Tian, X., Gu, Z., Zhang, H., Chen, R. and Luo, K. (2022), Stimuli-sensitive Linear-dendritic Block Copolymer-drug Prodrug As Nano-platform for Tumor Combination Therapy. Adv. Mater.. Accepted Author Manuscript 2108049, which has been published in final form at https://doi.org/10.1002/adma.202108049
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: RDF01
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
amphiphilic polymers
combination therapy
linear-dendritic block copolymers
nanomedicine
tumor-microenvironment-responsive polymers
MULTIFUNCTIONAL MICELLES
CANCER
DELIVERY
NANOCARRIERS
POLYMERS
NANOPARTICLES
PATHWAY
LACCASE
DESIGN
amphiphilic polymers
combination therapy
linear-dendritic block copolymers
nanomedicine
tumor-microenvironment-responsive polymers
amphiphilic polymer
combination therapy
linear-dendritic block copolymer
nanomedicine
tumor microenvironment-responsive
Nanoscience & Nanotechnology
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Publication Status: Published
Conference Place: Germany
Embargo Date: 2022-12-06
2022-12-06
Online Publication Date: 2021-12-07
Appears in Collections:Chemical Engineering
Faculty of Engineering