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Research Article

An FPS-ZM1-encapsulated zeolitic imidazolate framework as a dual proangiogenic drug delivery system for diabetic wound healing

Yi Sun1,2,§, Bingbo Bao1,§, Yu Zhu1,2,§, Junjie Shen1,2, Xuanzhe Liu1, Tao Gao1, Junqing Lin1, Tengli Huang1, Jia Xu1( ), Yimin Chai1( ), Xianyou Zheng1( )
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China

§ Yi Sun, Bingbo Bao, and Yu Zhu contributed equally to this work.

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Graphical Abstract

FZ@ZIF-67 nanoparticles for sustained dual delivery of Co ion and 4-chloro-N-cyclohexyl-N-(phenylmethyl)-benzamide (FPS-ZM1) to promote angiogenesisduring diabetic wound repair via hypoxia-inducible factor-1 alpha (HIF-1α)activation and receptor for advanced glycation end products (RAGE) inhibition.

Abstract

Inhibitors that target diabetes pathology-related signaling pathways have great therapeutic potential for diabetic wound healing. Metal–organic frameworks (MOFs) are increasingly popular drug delivery systems that have high loading capacity and can release their intrinsic metal ions to act as bioactive agents. In light of this, a receptor for advanced glycation end products (RAGE) inhibitor, 4-chloro-N-cyclohexyl-N-(phenylmethyl)-benzamide (FPS-ZM1), was loaded into a cobalt (Co)-based MOF (zeolitic imidazolate framework-67, ZIF-67) to fabricate FPS-ZM1 encapsulated ZIF-67 (FZ@ZIF-67) nanoparticles (NPs). As a result, FZ@ZIF-67 NPs could dually deliver Co ions and FPS-ZM1 in a controlled manner for over 14 days. Our in vitro study showed that FZ@ZIF-67 NPs not only enhanced angiogenesis by delivering Co ions but also released FPS-ZM1 to promote M2 macrophage polarization and attenuated high glucose (HG)- and/or inflammation-induced impairment of angiogenesis through RAGE inhibition. Moreover, in an in vivo study, FZ@ZIF-67 NPs markedly improved re-epithelialization, collagen deposition, neovascularization, and relieved inflammation in diabetic wounds in rats. This study not only provides a low-cost, effective, and synergistic proangiogenic bioactive agent but also demonstrates that targeting diabetes-related pathological signaling pathways is necessary to ameliorate vascularization impairment during diabetic wound healing.

Keywords

zeolitic imidazolate framework-67drug deliverydual-controlled releaseangiogenesisdiabetic wound

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Nano Research
Volume 15 Issue 6,
June 2022
Pages 5216-5229
DOI: 10.1007/s12274-022-4106-z
Cite this article:
Sun Y, Bao B, Zhu Y, et al. An FPS-ZM1-encapsulated zeolitic imidazolate framework as a dual proangiogenic drug delivery system for diabetic wound healing. Nano Research, 2022, 15(6): 5216-5229. https://doi.org/10.1007/s12274-022-4106-z
Topics:
Nano biology

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Received: 27 October 2021
Revised: 22 December 2021
Accepted: 22 December 2021
Published: 04 March 2022
© Tsinghua University Press 2022
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