Table 3.

Inflammation-targeting nanocarriers for treating cartilage defects in vivo.

Nanocarrier	Loaded Agents	Animal Model	Defect Type	Treatment	Follow-Up	Effect on Inflammation	Assessment Method	Ref.
chitosan-modified molybdenum disulfide nanosheets	dexamethasone	mouse	papain- induced OA	intra-articular injections every 3 days; near-infrared light exposure	4 weeks	IL-1β $\downarrow$ IL-8 $\downarrow$ TNF-α $\downarrow$ in the synovium	IHC staining	[121]
thermo-responsive chitosan oligosaccharide nanospheres conjugated with pluronic F127 grafting carboxyl group	kartogenin diclofenac	rat	ACLT, MM destabilization	intra-articular injections at weeks 7 and 10	8 weeks	COX-2 $\downarrow$ in the synovium	ELISA	[122]
poly(d,l-lactide-co-glycolide) nanoparticles	diacerein	rat	MIA- induced OA	single intra-articular injection	9 weeks	IL-1 $\downarrow$ IL-6 $\downarrow$ TNF-α $\downarrow$ MMP-3 $\downarrow$ MMP-13 $\downarrow$ COX-2 $\downarrow$ ADAMTS-5 $\downarrow$ IL-4 $\uparrow$ IL-10 $\uparrow$ in the whole blood	real-time PCR	[123]
hollow MnO2 nanoparticles modified with NH2-PEG-NH2	-	mouse	MM destabilization	intra-articular injections 3 times a week for 4 weeks	8 weeks	IL-1β $\downarrow$ IL-6 $\downarrow$ in the serum	ELISA	[124]
polyhydroxylated fullerene C60 (fullerol) nanoparticles	-	rat	MIA- induced OA	single intra-venous injection	3 weeks	reduced synovial inflammation	H&E staining	[125]
polyethylenimine conjugated with chondrocyte-affinity peptide	anti-Hif-2α siRNA	mouse	ACLT and MCL dissection	weekly intra-articular injections	7 weeks	reduced synovial inflammation IL-1β $\downarrow$ in the synovial fluid	H&E stainingELISA	[126]
methoxy poly(ethylene glycol)-b-poly (D,L-lactide) and PLGA-based nanoparticles	rebamipide	rat	MIA- induced OA	single intra-articular injection	4, 8 weeks	IL-1β$\downarrow$ IL-6$\downarrow$ TNF-α$\downarrow$ MMP-3$\downarrow$ MMP-13$\downarrow$ COX-2$\downarrow$ in the whole blood	real-time PCR	[127]
bilirubin grafted polylysine nanoparticles	IgG, berberine	rat	ACLT	intra-articular injections on day 35, 40, 45, 50, 55, and 60	65 days	reduced synovial inflammation TNF-α $\downarrow$ M1/M2 ratio $\downarrow$ in the synovium	H&E stainingIHC	[128]
nanoliposomes	resolvin D1	mouse	MM destabilization	intra-articular injections at weeks 1, 4, and 8	3 months	M1/M2 ratio $\downarrow$ in the synovium	IHC	[129]

ACLT—anterior cruciate ligament transection, anti-Hif-2α—hypoxia-inducible factor-2α, H&E—hematoxylin and eosin, IHC—immunohistochemistry, M1—proinflammatory macrophages, M2—anti-inflammatory macrophages, MCL—medial collateral ligament, MIA—monosodium iodoacetate, MM—medial meniscus, Ref.—reference.