Co‐Polymer Carrier with Dual Advantages of Cartilage‐Penetrating and Targeting Improves Delivery and Efficacy of MicroRNA Treatment of Osteoarthritis

Abstract

Osteoarthritis (OA) is a debilitating joint disease affecting nearly 400 million people with no efficient etiological therapies. OA is primarily identified by cartilage destruction, and gradual degeneration of the whole joint would happen when the OA progresses. Hence, cartilage has been identified as the primary therapeutic target of OA. Unfortunately, numerous barriers block the delivery of therapeutic agents into cartilage, including avascular traits and high hardness of the extracellular matrix. Herein, a cartilage‐targeting peptide (CAP) modified polyvinylamine (PVAm)‐ poly (lactic‐co‐glycolic acid) (PLGA) copolymer (CAP‐PVAm‐PLGA) is designed, which can form spherical nanoparticles with the r‐miR‐140 (CPP‐NPs). CPP‐NPs possessed enhanced mechanical properties due to the introduction of PLGA to vehicles. Meanwhile, CAP endowed the cartilage targeting which facilitated CPP‐NPs localization in cartilage. With such dual advantages, CPP‐NPs exhibited outstanding penetrability and accumulation in cartilage even subchondral bone, and can penetrate to a depth of 1000 µm into human cartilage. The degeneration area of cartilage is reduced by 65% and synovial inflammation score by 80% in OA mice, and the microarchitecture of subchondral bone is also ameliorated. These studies established a promising platform for therapeutic RNA delivery in OA therapy that overcame the cartilage barriers.

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy

“…The leakage from the joint or excretion from synovial blood vessels and lymphatic vessels are also the reasons for the short half-life and residence time in the joint [ 47 , 48 ]. Moreover, the dense packing of collagen and proteoglycans in joint tissue as well as the highly negatively charged glycosaminoglycans form a critical barrier needed to be penetrated in cartilage, which increases the difficulty in drug delivery [ 49 , 50 ]. The complexity of these factors makes chondrocyte-targeted drug delivery challenging.…”

“…The complexity of these factors makes chondrocyte-targeted drug delivery challenging. Up to now, various cartilage-targeting nanoplatforms have been developed which are beneficial in overcoming the dense collagen barrier and facilitating drug delivery [ 49 , 50 ]. Of note, the nanoparticles with a chondrocyte-affinity peptide can remain within cartilage for a prolonged period, making this an ideal substance for treating osteoarthritis.…”

Intra‐Articular Injection of Nanomaterials for the Treatment of Osteoarthritis: From Lubrication Function Restoration to Cell and Gene Therapy

“…Qian et al devised a putaminal RNA delivery vector, CPP-NP, capitalizing on the unique properties of cationic polymer poly vinylamine (PVAM) and chondrocyte-carrying affinity peptide (CAP). [333] The PVAM component effectively bound with the ECM via electrostatic interactions, while the incorporation of CAP enhanced cartilage targeting. Additionally, the integration of PLGA into the vector markedly improved its permeability through the dense ECM.…”

Nanotechnology-Boosted Biomaterials for Osteoarthritis Treatment: Current Status and Future Perspectives

“…66 Nanoparticles, liposomes, and other nanotechnology-boosted biomaterials can be used to deliver these non-coding RNAs to the target tissue, allowing for the modulation of gene expression and the improvement of OA pathology. 67 Overall, nanotechnology-boosted biomaterials provide a promising platform for the delivery of bioactive agents and genes for the treatment of OA. These biomaterials can improve the targeted delivery of therapeutic molecules, enhancing their therapeutic efficacy and reducing the risk of off-target effects.…”