Stimuli‐Sensitive Nanotherapies for the Treatment of Osteoarthritis

Abstract

Osteoarthritis (OA) is a common chronic inflammatory disease in the joints. It is one of the leading causes of disability with increasing morbidity, which has become one of the serious clinical issues. Current treatments would only provide temporary relief due to the lack of early diagnosis and effective therapy, and thus the replacement of joints may be needed when the OA deteriorates. Although the intra‐articular injection and oral administration of drugs are helpful for OA treatment, they are suffering from systemic toxicity, short retention time in joint, and insufficient bioavailability. Nanomedicine is potential to improve the drug delivery efficiency and targeting ability. In this focused progress review, the particle‐based drug loading systems that can achieve targeted and triggered release are summarized. Stimuli‐responsive nanocarriers that are sensitive to endogenous microenvironmental signals such as reactive oxygen species, enzymes, pH, and temperature, as well as external stimuli such as light for OA therapy are introduced in this review. Furthermore, the nanocarriers associated with targeted therapy and imaging for OA treatment are summarized. The potential applications of nanotherapies for OA treatment are finally discussed.

Recent Advances in Nano-Therapeutic Strategies for Osteoarthritis

“…Although many nanomaterial-based drugs and nanotherapeutic strategies have been investigated for OA therapy and many clinical studies on nanotherapeutic strategies are in progress ( Dejulius et al, 2021 ; Hunter et al, 2022 ), the nanomedicines currently in clinical trials are mainly non-functional nano-scale/micron-scale materials loaded with old drugs that are already commercially available for OA therapy. They mainly extend the retention time of the drugs and reduce systemic diffusion ( Wang et al, 2021 ). Some other functional nanotherapies for OA, with the extra properties of stimuli-responsive drug release, multiple regulatory mechanisms or other multifunctional characteristics, have attracted attention and are under investigation.…”

“…For example, targeting efficiency, bioavailability, and biological activity can be improved by this method. The targeted and stimuli-responsive nanotherapies, and many other combinations of functions, have also been investigated for OA treatment ( Wang et al, 2021 ). The specific inhibition of proliferation of activated macrophages and the clearance of high levels of ROS secreted by macrophages are important for the treatment of OA ( Pu et al, 2014 ; Yang et al, 2019 ).…”

“…OA is also associated with a variable degree of synovial inflammation that can be induced by the damage and dysfunction of the cartilage ( Scanzello, 2017 ). During the progression of OA, macrophages, synovial fibroblasts, and chondrocytes produce cytokines, chemokines, proteases, and reactive oxygen species (ROS) ( van den Bosch, 2021 ; Wang et al, 2021 ). Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor- α (TNF- α ) promote synovitis, inhibit chondrocyte viability, and induce the production of many proteases.…”

Benefits of Applying Nanotechnologies to Hydrogels in Efficacy Tests in Osteoarthritis Models—A Systematic Review of Preclinical Studies

“…Nanotechnology has been developed to mimic the nanoscale dimension of cartilaginous ECM and stimulate cell adhesion, migration, and proliferation, as well as to serve as local carriers of molecules for controlling their release, simultaneously protecting them from the harsh OA microenvironment and increasing their residence time in the joint. The precise control of the NP’s structure, degradation, and safety issues represent their main limits [ 21 , 22 , 23 ] NPs, defined as structures that reach dimensions of up to hundreds of nanometers [ 24 ], can be embedded into a hydrogel before its gelation or entrapped by gel swelling after gel formation [ 25 ]. These NP-enriched gel (NP-gels) formulations are of increasing interest because they can be used as drug delivery systems for anti-inflammatory drugs in OA, allowing controlled and prolonged release thanks to a higher retention in the joint than hydrogels alone.…”

Manipulation of ROS‐Responsiveness of Dextran with Thioether Side Chains

“…[ 6,7 ] However, when the balance is disrupted, the excessive generation of ROS will induce oxidative stress, resulting in irreversible damage to normal cells and tissues. [ 8,9 ] The oxidative stress is not only the mainly cause for inflammation, but closely related to the development of diseases such as cancer, cardiovascular disease or neurodegeneration. [ 10,11 ] Therefore, it is urgently needed to keep the ROS balance and prevent the abnormal inflammatory response of the body.…”