Microenvironment-responsive nanosystems for osteoarthritis therapy

Osteoarthritis (OA) represents an enduring and widespread global burden, causing significant morbidity and disability, whose pathology is characterized by persistent inflammation, progressive cartilage degeneration, abnormal bone homeostasis, and excessive synovial hyperplasia, resulting from its complex microenvironment. Unfortunately, current therapeutic approaches for OA remain suboptimal, prompting increased interest in advanced nanotechnology as a means to enhance therapeutic effects. In recent years, significant progress has been made in the development of versatile nanoplatforms designed to the specific microenvironment of OA, resulting in promising results and introducing the concept of "OA nanomedicine". Compared to the conventional therapies like non-steroidal anti-inflammatory drugs (NSAIDs), OA nanomedicine offers precise targeted, controllable and personalized ways for OA therapy, contributing to better outcomes. However, a comprehensive review consolidating the "OA nanomedicine" is currently absent from literature. Therefore, in this review, we aim to unravel the key pathological and microenvironmental characteristics of OA while summarizing the properties and advantages of nanosystems possessing microenvironment-reprogramming capabilities for OA therapy. First, we make a retrospection of the features of OA pathology and OA microenvironment. Furthermore, we provide an overview of the advances in OA nanomedicine. Eventually, we discuss the present challenges associated with OA nanomedicine and provide insights into its future prospects from a clinical-translational lens. By doing so, this review can foster and propel the successful development of OA nanomedicine, addressing the unmet needs in OA therapy.