Peptide-Driven Proton Sponge Nano-Assembly for Imaging and Triggering Lysosome-Regulated Immunogenic Cancer Cell Death.

Triggering lysosome-regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an "immune-cold" tumor "hot"-a key challenge faced by cancer immunotherapies. Proton sponge such as high-molecular-weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano-assemblies (PSNAs) with self-assembly controllable surface charge density and cell cytotoxicity are created. Such PSNAs are constructed via low-molecular-weight branched PEI covalently bound to self-assembling peptides carrying tetraphenylethene pyridinium (PyTPE, an aggregation-induced emission-based luminogen). Assembly of PEI assisted by the self-assembling peptide-PyTPE leads to enhanced surface positive charges and cell cytotoxicity of PSNA. The self-assembly tendency of PSNAs is further optimized by tuning hydrophilic and hydrophobic components within the peptide, thus resulting in the PSNA with the highest fluorescence, positive surface charge density, cell uptake, and cancer cell cytotoxicity. Systematic cell death mechanistic studies reveal that the lysosome rupturing-regulated pyroptosis and necroptosis are at least two causes of cell death. Tumor cells undergoing PSNA-triggered ICD activate immune cells, suggesting the great potential of PSNAs to trigger anticancer immunity.

Three-dimensional mapping of the greater palatine artery location and physiology.

OBJECTIVE: To develop a novel technique for localizing and reconstructing the greater palatine artery (GPA) using three-dimensional (3D) technology. METHODS: A miniaturized intraoral ultrasound transducer was used to imaging landmarks including the GPA, gingival margin (GM), and palatal masticatory mucosa (PMM). A 5-mm-thick solid hydrogel couplant was integrated to replace traditional ultrasound gel and avoid bubbles when moving the transducer. RESULTS: A panorama image provided the relative localization of landmarks including the GPA, PMM, and hard palate. Short- and long-axis imaging of GPA was performed in five subjects including 3D mapping of GPA branches and surrounding tissues in a volume of 10 mm × 8 mm × 10 mm. Full-mouth Doppler imaging was also demonstrated on both the dorsal and ventral tongue as well as buccal mucosa and sublingual region on two subjects. CONCLUSIONS: This study can measure the vertical distance from the GM to the GPA and depth from PMM to GPA and visualize the GPA localization in a 3D manner, which is critical to evaluate the available volume of palatal donor tissues and avoid sectioning of GPA during surgical harvesting of the tissues. Finally, the transducer's small size facilitates full-mouth Doppler imaging with the potential to improve the assessment, diagnosis, and management of oral mucosa.

3D-Bioprinted Phantom with Human Skin Phototypes for Biomedical Optics.

3D-bioprinted skin-mimicking phantoms with skin colors ranging across the Fitzpatrick scale are reported. These tools can help understand the impact of skin phototypes on biomedical optics. Synthetic melanin nanoparticles of different sizes (70-500 nm) and clusters are fabricated to mimic the optical behavior of melanosome. The absorption coefficient and reduced scattering coefficient of the phantoms are comparable to real human skin. Further the melanin content and distribution in the phantoms versus real human skins are validated via photoacoustic (PA) imaging. The PA signal of the phantom can be improved by: 1) increasing melanin size (3-450-fold), 2) increasing clustering (2-10.5-fold), and 3) increasing concentration (1.3-8-fold). Then, multiple biomedical optics tools (e.g., PA, fluorescence imaging, and photothermal therapy) are used to understand the impact of skin tone on these modalities. These well-defined 3D-bioprinted phantoms may have value in translating biomedical optics and reducing racial bias.