Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.

Degradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics.

Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous structures cannot be obtained by the traditional template-mediated strategies due to the inevitable hydrolytic reaction of semimetal compounds. Therefore, it is yet challenging to fabricate mesoporous semimetal nanostructures, not even mention controlling their pore sizes. Here we develop a facile and robust selective etching route to synthesize monodispersed mesoporous antimony nanospheres (MSbNSs). The pore sizes of MSbNSs are tunable by carefully controlling the partial oxidation of Sb nuclei and the selective etching of the as-formed Sb2O3. MSbNSs show a wide absorption from visible to second near-infrared (NIR-II) region. Moreover, PEGylated MSbNSs are degradable and the degradation mechanism is further explained. The NIR-II photothermal performance of MSbNSs is promising with a high photothermal conversion efficiency of ~44% and intensive NIR-II photoacoustic signal. MSbNSs show potential as multifunctional nanomedicines for NIR-II photoacoustic imaging guided synergistic photothermal/chemo therapy in vivo. Our selective etching process would contribute to the development of various semimetallic mesoporous structures and efficient multimodal nanoplatforms for theranostics.

Dedicated Photoacoustic Imaging Instrument for Human Periphery Blood Vessels: A New Paradigm for Understanding the Vascular Health.

A novel photoacoustic imaging system based on a semi-ring transducer array is proposed to image peripheral blood vessels. The system's penetration depth is deep (∼15 mm) with high spatial (∼200 µm) and temporal resolution. In a clinical study, volumetric photoacoustic data of limbs were obtained within the 50s (for a FOV of 15 cm × 4 cm) with the volunteers in the standing and sitting posture. Compared to the previous studies, our system has many advantages, including (1) Larger field of view; (2) Finer elevational and in-plane resolutions; (3) Enhanced 3D visualization of peripheral vascular networks; (4) Compact size and better portability. The 3D visualization and cross-sectional images of five healthy volunteers clearly show the vascular network and the system's ability to image submillimeter blood vessels. This high-resolution PA system has great potential for imaging human periphery vasculatures noninvasively in clinical research.

Antimony Nanopolyhedrons with Tunable Localized Surface Plasmon Resonances for Highly Effective Photoacoustic-Imaging-Guided Synergistic Photothermal/Immunotherapy.

Antimony (Sb), a typical group VA semimetal, has rarely been studied both experimentally and theoretically in plasmonic photothermal therapy, possibly due to the lack of effective morphology-controllable methods for the preparation of high-quality Sb nanocrystals. In this study, an effective ligand-guided growth strategy to controllably synthesize Sb nanopolyhedrons (Sb NPHs) with ultrahigh photothermal conversion efficiency (PTCE), good photothermal stability, as well as biocompatibility is presented. Furthermore, the modulation effect of different morphologies on localized surface plasmon resonance (LSPR) of Sb NPHs in experimentation is successfully observed. When the resonance frequency of the Sb NPHs is matched well with the excitation wavelength (808 nm), the PTCE of the Sb NPHs is as high as 62.1%, which is noticeably higher compared to most of the reported photothermal agents. The Sb NPHs also exhibit good photothermal stability. In addition, Sb-NPHs-based multifunctional nanomedicines are further constructed via loading 1-methyl-d-tryptophan on PEGylated Sb NPHs for a highly efficient photoacoustic-imaging-guided synergistic photothermal/immune-therapy of tumors in vivo. This work can stimulate further theoretical and experimental investigations of Sb NPHs and other semimetal nanomaterials regarding their LSPR properties and inspire various potential applications of semimetals in biomedicine and sensors.

Escherichia coli topoisomerase I is an iron and zinc binding protein.

Escherichia coli topoisomerase I (TopA) cleaves and rejoins one strand of double-stranded DNA to relax the negatively supercoiled DNA. Structurally, TopA contains an N-terminal catalytic fragment and a C-terminal zinc-binding region that is required for relaxation of the negatively supercoiled DNA. Here we report that E. coli TopA is an iron and zinc binding protein. The UV-Vis absorption measurements and metal content analyses reveal that TopA purified from E. coli cells grown in the rich LB medium contains both iron and zinc. However, TopA purified from E. coli cells grown in the M9 minimal medium has negligible amounts of zinc or iron and no topoisomerase activity. Nevertheless, supplement of exogenous zinc or iron in E. coli cells grown in the M9 minimal medium produces the zinc- or iron-bound TopA, respectively. Whereas the zinc-bound TopA is fully active to relax the negatively supercoiled DNA, the iron-bound TopA has little or no enzyme activity. Furthermore, excess iron in the M9 minimal medium is able to compete with the zinc binding in TopA in E. coli cells and attenuate the topoisomerase activity, suggesting that E. coli TopA may be modulated by iron and zinc binding in vivo.