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Synergistic disruption of metabolic homeostasis through hyperbranched poly(ethylene glycol) conjugates as nanotherapeutics to constrain cancer growth

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Pan et al., Advanced Materials 2022_Accepted Manuscript.pdfFile embargoed until 05 January 20231.53 MBAdobe PDF    Request a copy
Pan et al., Advanced Materials 2022_Supporting Information.pdfFile embargoed until 05 January 20235.96 MBAdobe PDF    Request a copy
Title: Synergistic disruption of metabolic homeostasis through hyperbranched poly(ethylene glycol) conjugates as nanotherapeutics to constrain cancer growth
Authors: Pan, D
Zheng, X
Zhang, L
Li, X
Zhu, G
Gong, M
Kopytynski, M
Zhou, L
Yi, Y
Zhu, H
Tian, X
Chen, R
Zhang, H
Gu, Z
Gong, Q
Luo, K
Item Type: Journal Article
Abstract: Combination therapy is a promising approach for effective treatment of tumors through synergistically regulating pathways. However, the synergistic effect is limited, likely by uncontrolled co-delivery of different therapeutic payloads in a single nanoparticle. Herein, we developed a combination nanotherapeutic by using two amphiphilic conjugates hyperbranched poly(ethylene glycol)-pyropheophorbide-a (Ppa) (HP-P) and hyperbranched poly(ethylene glycol)-doxorubicin (DOX) (HP-D) to construct co-assembly nanoparticles (HP-PD NPs) for controllably co-loading and co-delivering Ppa and DOX. In vitro and in vivo anti-tumor studies confirmed the synergistic effect of photodynamic therapy and chemotherapy from HP-PD NPs. Metabolic variations revealed that tumor suppression was associated with disruption of metabolic homeostasis, leading to reduced protein translation. Our study uncovers the manipulation of metabolic changes in tumor cells through disruption of cellular homeostasis using HP-PD NPs and provides a new insight into rational design of synergistic nanotherapeutics for combination therapy.
Issue Date: 10-Mar-2022
Date of Acceptance: 3-Jan-2022
URI: http://hdl.handle.net/10044/1/93819
DOI: 10.1002/adma.202109036
ISSN: 0935-9648
Publisher: Wiley
Journal / Book Title: Advanced Materials
Volume: 34
Issue: 10
Copyright Statement: This article is protected by copyright. All rights reserved
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
combination therapy
drug delivery
hyperbranched polymers
multiomics
self-assembly
tumor metabolism
NANOPARTICLES
LANDSCAPE
LIPOSOMES
DELIVERY
combination therapy
drug delivery
hyperbranched polymers
multiomics
self-assembly
tumor metabolism
hyperbranched polymer
self-assembly
computational simulation
multi-omics
tumor metabolism
combination therapy
Nanoscience & Nanotechnology
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Publication Status: Published
Embargo Date: 2023-01-05
Article Number: ARTN 2109036
Online Publication Date: 2022-01-06
Appears in Collections:Chemical Engineering
Faculty of Engineering