MMP-13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis
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Journal of Nanobiotechnology Open Access
RESEARCH
MMP‑13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis Qiumei Lan1†, Rongbin Lu1,2,4†, Haimin Chen1†, Yunfen Pang1, Feng Xiong1, Chong Shen1,3, Zainen Qin1,3*, Li Zheng1,2,3*, Guojie Xu1,2,4* and Jinmin Zhao1,2,3,4
Abstract Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA), which enables the development of stimulus-responsive drug delivery system with high specificity for OA. We herein demonstrate a nano-micelle based stimuli-responsive theranostic strategy with reporting and drug release controlled by acidic pH and MMP-13 for OA therapy. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an antiinflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro and vivo evidences. Keywords: MMP-13/pH sensitive, Cartilage targeting, Osteoarthritis, Theranostics Introduction As the most common chronic joint disease, osteoarthritis (OA) is regarded as the primary cause of disability among older adults [1, 2]. Systemic administration and intraarticular injections of glucocorticoids or non-steroidal anti-inflammatory drugs (NSAID) are hard to exert maximize therapeutic benefit due to the avascular tissue on articular surface, the poor bioavailability and short halflife of drug [3], and rapid drug clearance [4]. Significant efforts have focused on engineering drug delivery systems to prolong the retention time of drug in the joint [5, 6]. In recent years, emerging stimulus-responsive smart systems for targeted imaging and precision therapy have *Correspondence: [email protected]; [email protected]; [email protected] † Qiumei Lan, Rongbin Lu and Haimin Chen contributed equally to this work 1 Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China Full list of author information is available at the end of the article
attracted increasing interest, such as pH [7, 8], ROS [9] or NO [10] triggered drug release systems upon exposure to inflammation tissues, which not only prolonged drug release, but also increased specificity to tissue and cells. The selection of optimal stimulus for the smart drug delivery system is the key for OA therapy. During the process of OA, the increase of active protease can degrade the cartilage ECM, which is considered as the main cause of cartilage destruction, such as matrix metall
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