Induction of antitumor immunity in mice by the combination of nanoparticle-based photothermolysis and anti-PD-1 checkpoint inhibition.

Generation of durable tumor-specific immune response without isolation and expansion of dendritic cells or T cells ex vivo remains a challenge. In this study, we investigated the impact of nanoparticle-mediated photothermolysis in combination with checkpoint inhibition on the induction of systemic antitumor immunity. Photothermolysis based on near-infrared light-absorbing copper sulfide nanoparticles and 15-ns laser pulses combined with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) increased tumor infiltration by antigen-presenting cells and CD8-positive T lymphocytes in the B16-OVA mouse model. Moreover, combined photothermolysis, polymeric conjugate of the Toll-like receptor 9 agonist CpG, and αPD-1 significantly prolonged mouse survival after re-inoculation of tumor cells at a distant site compared to individual treatments alone in the poorly immunogenic syngeneic ID8-ip1-Luc ovarian tumor model. Thus, photothermolysis is a promising interventional technique that synergizes with Toll-like receptor 9 agonists and immune checkpoint inhibitors to enhance the abscopal effect in tumors.

Single-shot 3D photoacoustic computed tomography with a densely packed array for transcranial functional imaging.

Photoacoustic computed tomography (PACT) is emerging as a new technique for functional brain imaging, primarily due to its capabilities in label-free hemodynamic imaging. Despite its potential, the transcranial application of PACT has encountered hurdles, such as acoustic attenuations and distortions by the skull and limited light penetration through the skull. To overcome these challenges, we have engineered a PACT system that features a densely packed hemispherical ultrasonic transducer array with 3072 channels, operating at a central frequency of 1 MHz. This system allows for single-shot 3D imaging at a rate equal to the laser repetition rate, such as 20 Hz. We have achieved a single-shot light penetration depth of approximately 9 cm in chicken breast tissue utilizing a 750 nm laser (withstanding 3295-fold light attenuation and still retaining an SNR of 74) and successfully performed transcranial imaging through an ex vivo human skull using a 1064 nm laser. Moreover, we have proven the capacity of our system to perform single-shot 3D PACT imaging in both tissue phantoms and human subjects. These results suggest that our PACT system is poised to unlock potential for real-time, in vivo transcranial functional imaging in humans.