期刊
ADVANCED MATERIALS
卷 34, 期 10, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202109036
关键词
combination therapy; drug delivery; hyperbranched polymers; multiomics; self-assembly; tumor metabolism
类别
资金
- National Natural Science Foundation of China [52073193, 51873120, 81621003, 81801820, 82102197]
- 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYJC21013, ZYGD20007, ZYJC18011]
- China Postdoctoral Science Foundation [2018M643493]
- China National Postdoctoral Program for Innovation Talents [BX20200229]
- Fundamental Research Funds for the Central Universities
- NIHR Imperial Biomedical Research Centre (BRC)
In this study, a combination nanotherapeutic was developed by constructing co-assembled nanoparticles using two amphiphilic conjugates. In vitro and in vivo studies confirmed the synergistic effect of this nanotherapeutic in treating tumors, and metabolic variations revealed the association between tumor suppression and disruption of metabolic homeostasis.
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, a combination nanotherapeutic is developed 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 antitumor studies confirm the synergistic effect of photodynamic therapy and chemotherapy from HP-PD NPs. Metabolic variations reveal that tumor suppression is associated with disruption of metabolic homeostasis, leading to reduced protein translation. This 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 the rational design of synergistic nanotherapeutics for combination therapy.
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