» Articles » PMID: 34553427

Ubiquitination Flow Repressors: Enhancing Wound Healing of Infectious Diabetic Ulcers Through Stabilization of Polyubiquitinated Hypoxia-Inducible Factor-1α by Theranostic Nitric Oxide Nanogenerators

Overview
Journal Adv Mater
Date 2021 Sep 23
PMID 34553427
Citations 27
Authors
Affiliations
Soon will be listed here.
Abstract

Current treatments for diabetic ulcers (DUs) remain unsatisfactory due to the risk of bacterial infection and impaired angiogenesis during the healing process. The increased degradation of polyubiquitinated hypoxia-inducible factor-1α (HIF-1α) compromises wound healing efficacy. Therefore, the maintenance of HIF-1α protein stability might help treat DU. Nitric oxide (NO) is an intrinsic biological messenger that functions as a ubiquitination flow repressor and antibacterial agent; however, its clinical application in DU treatment is hindered by the difficulty in controlling NO release. Here, an intelligent near-infrared (NIR)-triggered NO nanogenerator (SNP@MOF-UCNP@ssPDA-Cy7/IR786s, abbreviated as SNP@UCM) is presented. SNP@UCM represses ubiquitination-mediated proteasomal degradation of HIF-1α by inhibiting its interaction with E3 ubiquitin ligases under NIR irradiation. Increased HIF-1α expression in endothelial cells by SNP@UCM enhances angiogenesis in wound sites, promoting vascular endothelial growth factor (VEGF) secretion and cell proliferation and migration. SNP@UCM also enables early detection of wound infections and ROS-mediated killing of bacteria. The potential clinical utility of SNP@UCM is further demonstrated in infected full-thickness DU model under NIR irradiation. SNP@UCM is the first reported HIF-1α-stabilizing advanced nanomaterial, and further materials engineering might offer a facile, mechanism-based method for clinical DU management.

Citing Articles

Emerging strategies for nitric oxide production and their topical application as nanodressings to promote diabetic wound healing.

Xia D, Guo Y, Xu R, Li N J Nanobiotechnology. 2025; 23(1):53.

PMID: 39881346 PMC: 11776289. DOI: 10.1186/s12951-025-03135-1.


Three-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritis.

Liu S, Jiang Y, Zhang Y, Lv K, Zhu J, Liu M J Nanobiotechnology. 2024; 22(1):727.

PMID: 39574125 PMC: 11583641. DOI: 10.1186/s12951-024-02953-z.


Cellular and molecular roles of reactive oxygen species in wound healing.

Hunt M, Torres M, Bachar-Wikstrom E, Wikstrom J Commun Biol. 2024; 7(1):1534.

PMID: 39562800 PMC: 11577046. DOI: 10.1038/s42003-024-07219-w.


Glucose oxidase: An emerging multidimensional treatment option for diabetic wound healing.

Liao Y, Zhang Z, Zhao Y, Zhang S, Zha K, Ouyang L Bioact Mater. 2024; 44:131-151.

PMID: 39484022 PMC: 11525048. DOI: 10.1016/j.bioactmat.2024.10.006.


Combined therapeutic strategy based on blocking the deleterious effects of AGEs for accelerating diabetic wound healing.

Yang Y, Huang S, Ma Q, Li N, Li R, Wang Y Regen Biomater. 2024; 11:rbae062.

PMID: 39323743 PMC: 11424028. DOI: 10.1093/rb/rbae062.