Ahmed M. Elbedwehy (한국표준과학연구원)

한빛사논문

조회138

Ahmed M. ElbedwehyAhmed M. Elbedwehy

한국표준과학연구원

J. Control. Release, Jul 17 2024, 373 S0168-3659(24)00453-X | https://doi.org/10.1016/j.jconrel.2024.07.022 ROS-responsive charge reversal mesoporous silica nanoparticles as promising drug delivery system for neovascular retinal diseases

Ahmed M. Elbedwehy ^a,b,c,1, Jun Wu ^d,e,1, Hee-Kyung Na ^b, Ahruem Baek ^b, Haejin Jung ^f, Ik Hwan Kwon ^b, Sang Won Lee ^b, Jeong Hun Kim ^d,e,g,h,i, Tae Geol Lee ^a,b

^aDepartment of Nano Science, Korea National University of Science and Technology (UST), Daejeon 34113, Republic of Korea

^bSafety Measurement Institute, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea

^cNanotechnology Center, Mansoura University, Mansoura 35516, Egypt

^dFight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea

^eDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea

^fFlow Cytometry Core Facility of Research Solution Center, Institute of Basic Science, Daejeon 34126, Republic of Korea

^gDepartment of Ophthalmology, Seoul National University Hospital, Seoul 03080, Republic of Korea

^hGlobal Excellence Center for Gene & Cell Therapy (GEC-GCT), Seoul National University Hospital, Seoul 03080, Republic of Korea

ⁱInstitute of Reproductive Medicine and Population, Seoul National University College of Medicine, Seoul 03080, Republic of Korea

¹These authors contributed equally to this work.

Correspondence to: Jeong Hun Kim, Tae Geol Lee

Abstract

Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w/w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to -25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-25)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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