A1 Refereed original research article in a scientific journal
Programmable NIR Responsive Nanocomposite Enables Noninvasive Intratympanic Delivery of Dexamethasone to Reverse Cisplatin Induced Hearing Loss
Authors: Mustaf, Rawand A.; Wang, Jiali; Xun, Mengzhao; Rosenholm, Jessica M.; Wang, Wuqing; Shu, Yilai; Zhang, Hongbo
Publisher: Wiley
Publishing place: HOBOKEN
Publication year: 2024
Journal: Advanced Science
Journal name in source: Advanced Science
Journal acronym: ADV SCI
Number of pages: 12
eISSN: 2198-3844
DOI: https://doi.org/10.1002/advs.202407067
Web address : https://doi.org/10.1002/advs.202407067
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/477090563
Local intratympanic drug delivery to the inner ear possesses significant otological clinical promise as cisplatin-induced hearing loss (CIHL) therapy, inducing significantly less side effects than systemic drug delivery. However, the multiple detoured barriers, round window membrane (RWM) and poorly controlled drug release hinder successful non-invasive drug delivery through intratympanic administration (IT). Here, a novel near-infrared (NIR) responsive nanocomposite functionalized with saponin, denoted gold nanorod@dexamethasone-mesoporous silica-saponin (AuNR@DEX-MS-saponin, NPs/DEX), is developed to enhance RWM permeation and to control the drug release spatiotemporally. First, the physiochemical properties and release profile of the synthesized nanocomposites are assessed, after which the biocompatibility of the nanocomposites and oto-protection against CIHL are shown in vitro and in vivo. The findings demonstrated that DEX is delivered to the inner ear with high efficiency through IT, due to the permeation enhancement effect of the nanocomposite. Moreover, the nanocomposite with low dose of DEX is highly effective in recovering CIHL, attenuating hair cell loss, and alleviating synaptic ribbon damage. These findings provide insight into NIR-responsive local delivery for inner ear illnesses.
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Funding information in the publication:
This work was supported by the Science and Technology Commission of Shanghai Municipality (21JC1401000), the Science and Technology Innovation Program of Hunan Province (2023RC4005), Fudan University (Grant yg2022-23), and the Research Fellow (Grant No.353146), Project (347897), Solution for Health Profile (336355), InFLAMES Flagship (337531) grants from Academy of Finland, Finland China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture. This study is part of the activities of the Åbo Akademi University Foundation (SÅA) funded Center of Excellence in Research “Materials-driven solutions for combating antimicrobial resistance (MADNESS)”. Transmission electron microscopy (JEM-1400 Plus) imaging facility was provided by the Laboratory of Electron Microscopy, University of Turku, Finland. Parts of the research used the Research Council of Finland Research Infrastructure “Printed Intelligence Infrastructure” (PII-FIRI).
