3D printing of plasmonic nanofocusing tip enabling high resolution, high throughput and high contrast optical near-field imaging.

Scanning near-field optical microscopy (SNOM) offers a means to reach a fine spatial resolution down to ~ 10 nm, but unfortunately suffers from low transmission efficiency of optical signal. Here we present design and 3D printing of a fiber-bound polymer-core/gold-shell spiral-grating conical tip that allows for coupling the inner incident optical signal to the outer surface plasmon polariton with high efficiency, which then adiabatically transport, squeeze, and interfere constructively at the tip apex to form a plasmonic superfocusing spot with tiny size and high brightness. Numerical simulations and optical measurements show that this specially designed and fabricated tip has 10% transmission efficiency, ~ 5 nm spatial resolution, 20 dB signal-to-noise ratio, and 7000 pixels per second fast scanning speed. This high-resolution, high throughput, and high contrast SNOM would open up a new frontier of high spatial-temporal resolution detecting, imaging, and monitoring of single-molecule physical, chemical, and biological systems, and deepen our understanding of their basic science in the single-molecule level.

Mechanisms of Reactive Oxygen Species Generated by Inorganic Nanomaterials for Cancer Therapeutics.

Recently, inorganic nanomaterials have received considerable attention for use in biomedical applications owing to their unique physicochemical properties based on their shapes, sizes, and surface characteristics. Photodynamic therapy (PDT), sonodynamic therapy (SDT), and chemical dynamic therapy (CDT), which are cancer therapeutics mediated by reactive oxygen species (ROS), have the potential to significantly enhance the therapeutic precision and efficacy for cancer. To facilitate cancer therapeutics, numerous inorganic nanomaterials have been developed to generate ROS. This mini review provides an overview of the generation mechanisms of ROS by representative inorganic nanomaterials for cancer therapeutics, including the structures of engineered inorganic nanomaterials, ROS production conditions, ROS types, and the applications of the inorganic nanomaterials in cancer PDT, SDT, and CDT.

Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth.

Photoimmunotherapy (PIT) has shown enormous potential in not only eliminating primary tumors, but also inhibiting abscopal tumor growth. However, the efficacy of PIT is greatly limited by tumor hypoxia, which causes the attenuation of phototherapeutic efficacy and is a feature of the immunosuppressive tumor microenvironment (TME). In this study, one type of brand-new artificial metalloprotein nanoanalogues is developed via reasonable integration of a "phototherapy-enzymatic" RuO2 and a model antigen, ovalbumin (OVA) for enhanced PIT of cancers, namely, RuO2 -hybridized OVA nanoanalogues (RuO2 @OVA NAs). The RuO2 @OVA NAs exhibit remarkable photothermal/photodynamic capabilities under the near-infrared light irradiation. More importantly, the photoacoustic imaging and immunofluorescence staining confirm that RuO2 @OVA NAs can remarkably alleviate hypoxia via in situ catalysis of hydrogen peroxide overexpressed in the TME to produce oxygen (O2 ). This ushers a prospect of concurrently enhancing photodynamic therapy and reversing the immunosuppressive TME. Also, OVA, as a supplement to the immune stimulation induced by phototherapy, can activate immune responses. Finally, further combination with the cytotoxic T-lymphocyte-associated protein 4 checkpoint blockade is reported to effectively eliminate the primary tumor and inhibit distant tumor growth via the abscopal effect of antitumor immune responses, prolonging the survival.

Natural Polyphenol-Vanadium Oxide Nanozymes for Synergistic Chemodynamic/Photothermal Therapy.

The selection of suitable nanozymes with easy synthesis, tumor specificity, multifunction, and high therapeutics is meaningful for tumor therapy. Herein, a facile one-step assembly approach was employed to successfully prepare a novel kind of natural polyphenol tannic acid (TA) hybrid with mixed valence vanadium oxide nanosheets (TA@VOx NSs). In this system, VOx is assembled with TA through metal-phenolic coordination interaction to both introduce superior peroxidase-like activity and high near infrared (NIR) absorption owing to partial reduction of vanadium from V5+ to V4+ . The presence of mixed valence vanadium oxide in TA@VOx NSs is proved to be the key for the catalytic reaction of hydrogen peroxide (H2 O2 ) to . OH, and the corresponding catalytic mechanism of H2 O2 by TA@VOx NSs is proposed. Benefitting from such peroxidase-like activity of TA@VOx NSs, the overproduced H2 O2 of the tumor microenvironment allows the realization of tumor-specific chemodynamic therapy (CDT). As a valid supplement to CDT, the NIR absorption enables TA@VOx NSs to have NIR light-mediated conversion ability for photothermal therapy (PTT) of cancers. Furthermore, in vitro and in vivo experiments confirmed that TA@VOx NSs can effectively inhibit the growth of tumors by synergistic CDT/PTT. These results offer a promising way to develop novel vanadium oxide-based nanozymes for enhanced synergistic tumor-specific treatment.

Receptor-Mediated and Tumor-Microenvironment Combination-Responsive Ru Nanoaggregates for Enhanced Cancer Phototheranostics.

Although phototherapy has been considered as an emerging and promising technology for cancer therapy, its therapeutic specificity and efficacy are severely limited by nonspecific uptake by normal tissues, tumor hypoxia, and so on. Herein, combination-responsive strategy (CRS) is applied to develop one kind of hyaluronic acid-hybridized Ru nanoaggregates (HA-Ru NAs) for enhanced cancer phototherapy via the reasonable integration of receptor-mediated targeting (RMT) and tumor-microenvironment responsiveness (TMR). In this nanosystem, the HA component endows HA-Ru NAs with RMT characteristic to selectively recognize CD44-overexpressing cancer cells, whereas the Ru nanocomponent makes HA-Ru NAs have TMR therapy activity. Specially, the Ru nanocomponent not only has near-infrared-mediated photothermal and photodynamic functions but also can catalyze H2O2 in tumor tissue to produce O2 for the alleviation of tumor hypoxia and toxic •OH for chemodynamic therapy. Benefitting from these, HA-Ru NAs can be considered as a promising kind of CRS nanoplatforms for synergistic photothermal/photodynamic/chemodynamic therapies of cancer, which will not only effectively improve the phototherapeutic specificity and efficacy but also simplify the therapeutic nanosystems. Meanwhile, HA-Ru NAs can serve as a photoacoustic and computed tomography imaging contrast agent to monitor tumors. Such CRS nanoplatforms hold significant potential in improving therapeutic specificity and efficacy for enhanced cancer phototheranostics.