Table 3.

Summary of current acoustic systems for RA diagnosis and therapy.

Acoustic diagnosis and therapy	Nano-system	Generation NPs	Targets	Animal model	Mechanisms	Effects	Key features	Limitations	Refs.
PA	IL4@AuNCs	Au NCs	Macrophage	AIA mice	1TNF-α, IL-1β, and IL-6↓ 2iNOS↓ Arg-1↑ 3Sox-9, Col-2, and Aggrecan↑ MMP-9↓	Regulates the inflammatory microenvironment, promotes macrophage M2 polarization, and reduces inflammatory factor secretion.	High optical absorption and signal enhancement; multimodal imaging compatibility.	Potential long-term clearance issues.	[29]
	M@P-siRNAsT/I	PBNPs	Macrophage	CIA mice	1TNF-α, IL-6, MMP3, MMP13, and VEGF↓ 2O2↑ HIF-α and ROS↓	Improves joint erosion, hypoxia inhibition, and anti-inflammation.	Excellent photostability; enzyme-like activity; good biosafety.	Metabolic pathway requires further clarification; high cost.	[30]
	GF-TF	MPNs	Macrophage	CIA mice	TNF-α, IL-1β, and IL-6↓	Significantly inhibits inflammatory synovitis, protects joint cartilage, prevents bone erosion, and reduces inflammatory cytokine secretion.	Real-time monitoring of drug release; structure-responsive signal changes; MRI imaging capability.	Limited signal stability.	[31]
	MNP-PEG-RGD	MNPs	Vascular endothelial cell	AIA mice	–	The PA signals produced by nanoparticles allow for real-time assessment of therapeutic response in RA.	Good biocompatibility; high optical stability.	Potential non-specific uptake.	[32]
	M-TDNPs	TT-BTA	Macrophage	CIA mice	1TNF-α, IL-1β, and IL-6↓ 2NO↓	Allows real-time RA monitoring and grading while mitigating inflammation, cartilage damage, and promoting bone repair.	NO-responsive "turn-on" signal; efficient PA conversion; good biocompatibility and stability.	Complex synthesis; difficult scale-up production.	[33]
	TCZ-PNPs	PBDTBBT	–	CIA mice	–	Alleviates forepaw inflammation in CIA mice, reduces synovial hyperplasia, immune cell infiltration, and bone destruction, while enabling adjunctive NIR-II PMI for RA therapeutic monitoring.	First example of NIR-II PMI for RA theranostics; intense NIR-II absorption and high photostability; High penetration depth and SNR; good biosafety.	Complex synthesis and high cost.	[34]
PA/FL	FA-CF-NP	Cptnc-4F (CF)	Macrophage	CIA mice	–	Specifically targets macrophages for monitoring early-stage macrophage alterations and diagnosing RA progression.	Early diagnostic capability; low background interference; higher sensitivity.	Lacks disease responsiveness; monitoring-only function without therapeutic effect.	[35]
	GAC	Cypate	Neutrophils	CIA mice	TNF-α, IL-1β, and IL-6↓ IL-10↑	Guides RA photothermal therapy while dynamically monitoring inflammatory recruitment, downregulating pro-inflammatory cytokines in serum.	Dual NIR peaks 725 nm and 800 nm) enabling flexible excitation wavelength choice.	Limited stability; prone to photodegradation and aggregation-caused FL quenching.	[36]
	TPC-U@HAT	TPY	Macrophage	ZIA mice + CIA mice	1TNF-α, IL-1β, and IL-6↓ 2NLRP3, NF-κB p65, and pSTAT1↓	Alleviates joint inflammation, attenuates MSOT/FL signals, suppresses paw swelling, reduces articular cartilage erosion, and improves motor function in mice.	Specific activation with low background and high SNR; enhanced sensitivity; MSOT imaging enabling signal source resolution beyond detection.	Probe stability limitations; high equipment cost.	[37]
	FPA	FPA	–	–	–	With mitochondrial targeting and passive accumulation, the FPA probe enables spatiotemporal HNO imaging in arthritic mice upon local injection.	First probe developed for in vivo HNO-activated imaging of inflammatory diseases.	Unknown long-term biodistribution, clearance, and chronic toxicity.	[38]
SDT	IGG	IGG	MH7A	–	ROS↑	Significantly reduces mitochondrial membrane potential, markedly increases ROS generation, and induces apoptosis in MH7A cells.	First use of SDT in anti-arthritis research.	Poor photostability; non-specific distribution.	[39]
	Bi NTs-ZnPP/HSA	ZnPP	SPARC	CIA mice	1TNF-α, IL-1β, and IL-6↓ 2O2↑ HIF-α, VEGF, and MMP-3↓ 3ROS and Bax↑ Bcl-2↓	Alleviates bone erosion, joint swelling, and synovitis while reducing hypoxia response and pro-inflammatory cytokine expression, promoting apoptosis over necrosis.	HO-1 inhibition for enhanced SDT efficacy; high drug loading capacity; good biocompatibility.	Challenging scale-up preparation.	[40]
	Fe3O4-PPIX@Mφs	PPIX	Macrophage	CIA mice	1TNF-α, IL-1β, and IL-6↓ 2ROS and ‧OH↑	Significantly reduces joint swelling, ameliorates synovial hyperplasia, cartilage damage, and inflammatory cell infiltration, while decreasing pro-inflammatory cytokine levels in serum.	Catalyzes ·OH generation from H2O2 via Fenton reaction, synergistic with SDT; good biocompatibility; FL imaging capability.	Limited photostability.	[41]
	Rh/SPX-HSA	SPX	RAFLS	CIA mice	1TNF-α, IL-1β, and IL-6↓ 2O2↑ HIF-α, and VEGF↓ 3‧OH, 1O2, Caspase-3, Cleaved Caspase-3, and Bax↑ Bcl-2↓	Alleviates joint swelling, reduces bone erosion, mitigates articular hypoxia and angiogenesis, and decreases serum pro-inflammatory cytokine levels.	Improves hypoxic microenvironment to synergistically enhance SDT efficacy, with dual POD-like and CAT-like activities.	The broad-spectrum antibacterial agent SPX can induce side effects in non-target tissues; Unknown metabolic pathway and long-term toxicity.	[42]
	BMCC NPs	Cu(I)Ce6	RAFLS	CIA mice	O2, 1O2, and ‧OH↑	Reduces clinical joint scores, decreases joint and paw thickness, mitigates bone erosion and cartilage damage, and suppresses synovial hyperplasia.	SDT activated by weak acid and cysteine, reducing off-target toxicity; hypoxia alleviation enhances SDT efficacy.	Long-term in vivo metabolic pathway is unknown; potential biocompatibility risks remain unclear.	[43]
	CUR/O2-MC	CUR	–	CIA rats	1ROS and O2↑ 2HIF-α, IL-6, and TNF-α↓	Ameliorates joint swelling, bone erosion, and synovitis in CIA rats, accompanied by reduced inflammatory factors and HIF-1α.	Natural sonosensitizer with good biosafety; O2 generation enhances SDT efficacy.	Low curcumin bioavailability; unclear in vivo release kinetics of microcapsules.	[44]