Room temperature liquid metals (LMs) represent a class of emerging multifunctional materials with attractive novel properties. Here, we show that photopolymerized LMs present a unique nanoscale capsule structure characterized by high water dispersibility and low toxicity. We also demonstrate that the LM nanocapsule generates heat and reactive oxygen species under biologically neutral near-infrared (NIR) laser irradiation. Concomitantly, NIR laser exposure induces a transformation in LM shape, destruction of the nanocapsules, contactless controlled release of the loaded drugs, optical manipulations of a microfluidic blood vessel model and spatiotemporal targeted marking for X-ray-enhanced imaging in biological organs and a living mouse. By exploiting the physicochemical properties of LMs, we achieve effective cancer cell elimination and control of intercellular calcium ion flux. In addition, LMs display a photoacoustic effect in living animals during NIR laser treatment, making this system a powerful tool for bioimaging.

Photoacoustic (PA) imaging holds great promise for preclinical research and clinical practice. However, most studies rely on the laser wavelength in the first near-infrared (NIR) window (NIR-I, 650-950 nm), while few studies have been exploited in the second NIR window (NIR-II, 1000-1700 nm), mainly due to the lack of NIR-II absorbing contrast agents. We herein report the synthesis of a broadband absorbing PA contrast agent based on semiconducting polymer nanoparticles (SPN-II) and apply it for PA imaging in NIR-II window. SPN-II can absorb in both NIR-I and NIR-II regions, providing the feasibility to directly compare PA imaging at 750 nm with that at 1064 nm. Because of the weaker background PA signals from biological tissues in NIR-II window, the signal-to-noise ratio (SNR) of SPN-II resulted PA images at 1064 nm can be 1.4-times higher than that at 750 nm when comparing at the imaging depth of 3 cm. The proof-of-concept application of NIR-II PA imaging is demonstrated in in vivo imaging of brain vasculature in living rats, which showed 1.5-times higher SNR as compared with NIR-I PA imaging. Our study not only introduces the first broadband absorbing organic contrast agent that is applicable for PA imaging in both NIR-I and NIR-II windows but also reveals the advantages of NIR-II over NIR-I in PA imaging.

We have developed a class of blackbody materials, i. e., hyperbranched Au plasmonic blackbodies (AuPBs), of compact sizes (<50 nm). The AuPBs were prepared in a seedless and surfactant-free approach based on the use of mussel-inspired dopamine. Strong intraparticle plasmonic coupling among branches in close proximity leads to intense and uniform broadband absorption across 400-1350 nm. The blackbody absorption imparts the compact AuPB with a superior photothermal efficiency of >80% and closely matched photothermal activity in the first near-infrared (NIR-I) and the second near-infrared (NIR-II) spectral windows, making it a rare broadband theranostic probe for integrated photoacoustic imaging and photothermal therapy (PTT). Our comparative study, using the same probe, has demonstrated that the improved PTT outcome of NIR-II over NIR-I primarily results from its higher maximum permission exposure (MPE) rather than the deeper tissue penetration favored by longer wavelengths. The compact plasmonic broadband nanoabsorbers with tailored surface properties hold potential for a wide spectrum of light-mediated applications.

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window (1000-1700 nm) holds great promise for deep-tissue diagnosis due to the reduced light scattering and minimized tissue absorption in this region; however, exploration of such non-invasive imaging technique is greatly constrained by the lack of biodegradable NIR-II absorbing agents. We herein report the first series of metabolizable NIR-II PA agents based on semiconducting polymer nanoparticles (SPNs). Such completely organic nanoagents are composed of a πconjugated yet oxidizable optical polymer as the PA generator and a hydrolysable amphiphilic polymer as the particle matrix to provide water solubility. The obtained SPNs are readily degraded by myeloperoxidase and lipase abundant in phagocytes, transforming themselves from the non-fluorescent nanoparticles (30 nm) into the NIR fluorescent ultra-small metabolites (~ 1 nm). As such, these NIR-II PA nanoagents can be effectively cleared out via both hepatobiliary and renal excretions after systematic administration, leaving no toxicity to living mice. More importantly, the nanoagents possess the highest photothermal conversion efficiencies among all reported organic materials, and emit bright PA signals at 1064 nm, enabling sensitive NIR-II PA imaging of both subcutaneous tumor and deep brain vasculature shielded by intact skull in living mice at a low systematic dosage. This study thus provides a generalized molecular design towards organic metabolizable semiconducting materials for biomedical optical applications in the NIR-II windows.

Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression.

Purpose:To evaluate in vivo sentinel lymph node (SLN) mapping by using photoacoustic and ultrasonographic (US) imaging with a modifi ed clinical US imaging system. Materials and Methods:Animal protocols were approved by the Animal Studies Committee. Methylene blue dye accumulation in axillary lymph nodes of seven healthy Sprague-Dawley rats was imaged by using a photoacoustic imaging system adapted from a clinical US imaging system. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken or turkey breast on top of the rat skin surface. Three-dimensional photoacoustic images were acquired by mechanically scanning the US transducer and light delivery fi ber bundle along the elevational direction. Results:Photoacoustic images of rat SLNs clearly help visualization of methylene blue accumulation, whereas coregistered photoacoustic/US images depict lymph node positions relative to surrounding anatomy. Twenty minutes following methylene blue injection, photoacoustic signals from SLN regions increased nearly 33-fold from baseline signals in preinjection images, and mean contrast between SLNs and background tissue was 76.0 6 23.7 (standard deviation). Methylene blue accumulation in SLNs was confi rmed photoacoustically by using the optical absorption spectrum of the dye. Three-dimensional photoacoustic images demonstrate dynamic accumulation of methylene blue in SLNs after traveling through lymph vessels. Conclusion:In vivo photoacoustic and US mapping of SLNs was successfully demonstrated with a modifi ed clinical US scanner. These results raise confi dence that photoacoustic and US imaging can be used clinically for accurate, noninvasive imaging of SLNs for axillary lymph node staging in breast cancer patients.q RSNA, 2010

Abstract. We present a novel temperature-sensing technique using thermoacoustic and photoacoustic measurements. This noninvasive method has been demonstrated using a tissue phantom to have high temporal resolution and temperature sensitivity. Because both photoacoustic and thermoacoustic signal amplitudes depend on the temperature of the source object, the signal amplitudes can be used to monitor the temperature. A temperature sensitivity of 0.15°C was obtained at a temporal resolution as short as 2 s, taking the average of 20 signals. The deep-tissue imaging capability of this technique can potentially lead us to in vivo temperature monitoring in thermal or cryogenic applications.

Organic semiconducting nanoprobes doped with bulky borane can undergo specific activation by ONOO even at tumor-relevant acidic pH (6.8), permitting in vivo ratiometric photoacoustic imaging of ONOO in the tumor environment of living mice.