Transcytosis-Inducing Multifunctional Albumin Nanomedicines with Deep Penetration Ability for Image-Guided Solid Tumor Treatment.

Transcytosis is an active transcellular transportation pathway that has garnered interest for overcoming the limited deep penetration of nanomedicines in solid tumors. In this study, a charge-convertible nanomedicine that facilitates deep penetration into solid tumors via transcytosis is designed. It is an albumin-based calcium phosphate nanomedicine loaded with IR820 (mAlb-820@CaP) for high-resolution photoacoustic imaging and enhanced photothermal therapy. Biomineralization on the surface stabilizes the albumin-IR820 complex during circulation and provides calcium ions (Ca2+ ) for tissue penetration on degradation in an acidic environment. pH-triggered transcytosis of the nanomedicine enabled by caveolae-mediated endocytosis and calcium ion-induced exocytosis in 2D cellular, 3D spheroid, and in vivo tumor models is demonstrated. Notably, the extravasation and penetration ability of the nanomedicine is observed in vivo using a high-resolution photoacoustic system, and nanomedicine shows the most potent photothermal antitumor effect in vivo. Overall, the strategy provides a versatile theragnosis platform for both noninvasive photoacoustic imaging and high therapeutic efficiency resulting from deep penetration of nanomedicine.

Surfactant-Stripped Semiconducting Polymer Micelles for Tumor Theranostics and Deep Tissue Imaging in the NIR-II Window.

Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.

In Vivo Dual-Modal Photoacoustic and Ultrasound Imaging of Sentinel Lymph Nodes Using a Solid-State Dye Laser System.

Photoacoustic imaging (PAI) is being actively investigated as a non-invasive and non-radioactive imaging technique for sentinel lymph node (SLN) biopsy. By taking advantage of optical and ultrasound imaging, PAI probes SLNs non-invasively with methylene blue (MB) in both live animals and breast cancer patients. However, these PAI systems have limitations for widespread use in clinics and commercial marketplaces because the lasers used by the PAI systems, e.g., tunable liquid dye laser systems and optical parametric oscillator (OPO) lasers, are bulky in size, not economical, and use risky flammable and toxic liquid dyes. To overcome these limitations, we are proposing a novel dual-modal photoacoustic and ultrasound imaging system based on a solid-state dye laser (SD-PAUSI), which is compact, convenient, and carries far less risk of flammability and toxicity. Using a solid-state dye handpiece that generates 650-nm wavelength, we successfully imaged the MB tube positioned deeply (~3.9 cm) in chicken breast tissue. The SLNs were also photoacoustically detected in the in vivo rats beneath a 2.2-cm-thick layer of chicken breast, which is deeper than the typical depth of SLNs in humans (1.2 ± 0.5 cm). Furthermore, we showed the multispectral capability of the PAI by switching the dye handpiece, in which the MB-dyed SLN was selectively highlighted from the surrounding vasculature. These results demonstrated the great potential of the SD-PAUSI as an easy but effective modality for SLN detection.

Detection of micro inclusions in steel sheets using high-frequency ultrasound speckle analysis.

With the increasing need for steel sheet quality assurance, the detection of micro-scaled inclusions in steel sheets has become critical. Many techniques have been explored to detect inclusions, e.g., visual inspection, radiography, magnetic testing, and ultrasound. Among these methods, ultrasound (US) is the most commonly used non-destructive testing (NDT) method due to its ease of use and deep penetration depth. However, ultrasound currently cannot be used for detecting the micro-scaled inclusions due to low spatial resolution, e.g., less than 30 µm, which are the key important factors causing the cracks in the high-quality steel sheets. Here, we demonstrate a high-resolution US imaging (USI) using high-frequency US transducers to image micro inclusions in steel sheets. Our system utilizes through-transmission USI and identifies ultrasound scattering produced by the inclusions. We first ultrasonically imaged the artificial flaws induced by the laser on the steel sheet surface for validating the system. We then imaged the real inclusions in the steel sheets formed during manufacturing processes and analyzed them to derive quantitative parameters related to the number of micro-scaled inclusions. Our results confirm that inclusions less than 30 µm can be identified using our high-resolution USI modality and has the potential to be used as an effective tool for quality assurance of the steel sheets.

A photoacoustic finder fully integrated with a solid-state dye laser and transparent ultrasound transducer.

The standard-of-care for evaluating lymph node status in breast cancers and melanoma metastasis is sentinel lymph node (SLN) assessment performed with a handheld gamma probe and radioisotopes. However, this method inevitably exposes patients and physicians to radiation, and the special facilities required limit its accessibility. Here, we demonstrate a non-ionizing, cost-effective, handheld photoacoustic finder (PAF) fully integrated with a solid-state dye laser and transparent ultrasound transducer (TUT). The solid-state dye laser handpiece is coaxially aligned with the spherically focused TUT. The integrated finder readily detected photoacoustic signals from a tube filled with methylene blue (MB) beneath a 22 mm thick layer of chicken tissue. In live animals, we also photoacoustically detected both SLNs injected with MB and subcutaneously injected melanomas. We believe that our radiation-free and inexpensive PAF can play a vital role in SLN assessment.