Defect-rich titanium nitride nanoparticle with high microwaveacoustic conversion efficiency for thermoacoustic imaging-guided deep tumor therapy

Pulse microwave excite thermoacoustic(TA)shockwave to destroy tumor cells in situ.This has promising applications for precise tumor therapy in deep tissue.Nanoparticle(NP)with high microwave-acoustic conversion is the key to enhance the efficiency of therapy.In this study,we firstly developed defect-rich titanium nitride nanoparticles(TiN NPs)for pulse microwave excited thermoacoustic(MTA)therapy.Due to a large number of local structural defects and charge carriers,TiN NPs exhibit excellent electromagnetic absorption through the dual mechanisms of dielectric loss and resistive loss.With pulsed microwave irradiation,it efficiently converts the microwave energy into shockwave via thermocavitation effect,achieving localized mechanical damage of mitochondria in the tumor cell and yielding a precise antitumor effect.In addition to the therapeutic function,the NP-mediated TA process also generates images that provide valuable information,including tumor size,shape,and location for treatment planning and monitoring.The experimental results showed that the TiN NPs could be efficiently accumulated in the tumor via intravenous infusion.With the deep tissue penetration characteristics of microwave,the proposed TiN-mediated MTA therapy effectively and precisely cures tumors in deep tissue without any detectable side effects.The results indicated that defect-rich TiN NPs are promising candidates for tumor therapy.

Polarization microwave-induced thermoacoustic imaging for quantitative characterization of deep biological tissue microstructures

Polarization optical imaging can be used to characterize anisotropy in biological tissue microstructures and has been demonstrated to be a powerful tool for clinical diagnosis. However, the approach is limited by an inability to image targets deeper than ~1 mm due to strong optical scattering in biological tissues. As such, we propose a novel polarization microwave-induced thermoacoustic imaging(P-MTAI) technique to noninvasively detect variations in deep tissue by exploiting the thermoacoustic signals induced by four pulsed microwaves of varying polarization orientations. The proposed P-MTAI method overcomes the penetration limits of conventional polarization optical imaging and provides submillimeter resolution over depths of several centimeters. As part of the paper, the structural characteristics of tissues were quantified using a new parameter, the degree of microwave absorption anisotropy. P-MTAI was also applied to the noninvasive detection of morphological changes in cardiomyocytes as they transitioned from ordered to disordered states, providing a potential indication of myocardial infarction.

Photoacoustic-immune therapy with a multi-purpose black phosphorus-based nanoparticle

Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue,inhibit metastases,and prevent tumor relapses,are the ultimate goals in the battle against cancer.We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic(PA)therapy with checkpoint-blockade immunotherapy.With the mitochondria targeting nanoparticle,PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor.More importantly,PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses.When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4,the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy.Furthermore,the number of memory T cells detected in the spleen is increased,and these cells inhibit tumor recurrence.This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity.