Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis

Abstract Alkali burns are potentially blinding corneal injuries. Due to the lack of available effective therapies, the prognosis is poor. Thus, effective treatment methods for corneal alkali burns are urgently needed. Codelivery nanoparticles (NPs) with characteristics such as high bioavailability a...

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Main Authors: Xiaojing Xiong, Huiting Jiang, Yukun Liao, Yangrui Du, Yu Zhang, Zhigang Wang, Minming Zheng, Zhiyu Du
Format: Article
Language:English
Published: Wiley 2023-03-01
Series:Bioengineering & Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/btm2.10499
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author Xiaojing Xiong
Huiting Jiang
Yukun Liao
Yangrui Du
Yu Zhang
Zhigang Wang
Minming Zheng
Zhiyu Du
author_facet Xiaojing Xiong
Huiting Jiang
Yukun Liao
Yangrui Du
Yu Zhang
Zhigang Wang
Minming Zheng
Zhiyu Du
author_sort Xiaojing Xiong
collection DOAJ
description Abstract Alkali burns are potentially blinding corneal injuries. Due to the lack of available effective therapies, the prognosis is poor. Thus, effective treatment methods for corneal alkali burns are urgently needed. Codelivery nanoparticles (NPs) with characteristics such as high bioavailability and few side effects have been considered effective therapeutic agents for ocular diseases. In this study, we designed a new combination therapy using liposomes and trimethyl chitosan (TMC) for the codelivery of insulin (INS) and vascular endothelial growth factor small interfering RNA (siVEGF) to treat alkali‐burned corneas. We describe the preparation and characterization of siVEGF‐TMC‐INS‐liposome (siVEGF‐TIL), drug release characteristics, intraocular tracing, pharmacodynamics, and biosafety. We found that siVEGF‐TIL could inhibit oxidative stress, inflammation, and the expression of VEGF in vitro and effectively maintained corneal transparency, accelerated epithelialization, and inhibited corneal neovascularization (CNV) in vivo. Morever, we found that the therapeutic mechanism of siVEGF‐TIL is possibly relevant to the inhibition of the ferroptosis signaling pathway by metabolomic analysis. In general, siVEGF‐TIL NPs could be a safe and effective therapy for corneal alkali burn.
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spelling doaj.art-881fc8c9ec5b4cc090d898ee116ad9552023-03-14T16:53:48ZengWileyBioengineering & Translational Medicine2380-67612023-03-0182n/an/a10.1002/btm2.10499Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosisXiaojing Xiong0Huiting Jiang1Yukun Liao2Yangrui Du3Yu Zhang4Zhigang Wang5Minming Zheng6Zhiyu Du7Department of Ophthalmology Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Ophthalmology Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Ophthalmology Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Ophthalmology Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Ophthalmology Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaChongqing Key Laboratory of Ultrasound Molecular Imaging Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Ophthalmology Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Ophthalmology Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaAbstract Alkali burns are potentially blinding corneal injuries. Due to the lack of available effective therapies, the prognosis is poor. Thus, effective treatment methods for corneal alkali burns are urgently needed. Codelivery nanoparticles (NPs) with characteristics such as high bioavailability and few side effects have been considered effective therapeutic agents for ocular diseases. In this study, we designed a new combination therapy using liposomes and trimethyl chitosan (TMC) for the codelivery of insulin (INS) and vascular endothelial growth factor small interfering RNA (siVEGF) to treat alkali‐burned corneas. We describe the preparation and characterization of siVEGF‐TMC‐INS‐liposome (siVEGF‐TIL), drug release characteristics, intraocular tracing, pharmacodynamics, and biosafety. We found that siVEGF‐TIL could inhibit oxidative stress, inflammation, and the expression of VEGF in vitro and effectively maintained corneal transparency, accelerated epithelialization, and inhibited corneal neovascularization (CNV) in vivo. Morever, we found that the therapeutic mechanism of siVEGF‐TIL is possibly relevant to the inhibition of the ferroptosis signaling pathway by metabolomic analysis. In general, siVEGF‐TIL NPs could be a safe and effective therapy for corneal alkali burn.https://doi.org/10.1002/btm2.10499corneal alkali burnferroptosis inhibitioninsulinnanomedicinesiVEGF
spellingShingle Xiaojing Xiong
Huiting Jiang
Yukun Liao
Yangrui Du
Yu Zhang
Zhigang Wang
Minming Zheng
Zhiyu Du
Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis
Bioengineering & Translational Medicine
corneal alkali burn
ferroptosis inhibition
insulin
nanomedicine
siVEGF
title Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis
title_full Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis
title_fullStr Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis
title_full_unstemmed Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis
title_short Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis
title_sort liposome trimethyl chitosan nanoparticles codeliver insulin and sivegf to treat corneal alkali burns by inhibiting ferroptosis
topic corneal alkali burn
ferroptosis inhibition
insulin
nanomedicine
siVEGF
url https://doi.org/10.1002/btm2.10499
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