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