The development of fluorophores and molecular probes for the second near-infrared biological window (NIR-II, 1000-1700 nm) represents an important, newly emerging and dynamic field in molecular imaging, chemical biology and materials chemistry. Because of reduced scattering, minimal absorption and negligible autofluorescence, NIR-II imaging provides high resolution, a high signal-to-noise ratio, and deep tissue penetration capability. Among various state-of-the-art bioimaging modalities, one of the greatest challenges in developing novel probes is to achieve both high resolution and sensitivity. The chemical design and synthesis of NIR-II fluorophores suitable for multimodal imaging is thus emerging as a new and powerful strategy for obtaining high-definition images. NIR-II fluorophores may convert NIR-II photons into heat for photothermal therapy and be excited by NIR-II light to produce singlet oxygen for photodynamic therapy. The presence of simultaneous diagnostic and therapeutic capabilities in a single probe can be used for precise treatment. In this review, we have focused on recent advances in the chemical design and synthesis of NIR-II fluorophores from small organic molecules to organic and inorganic nanoparticles, and we have further discussed recent advances and key operational differences in reported NIR-II imaging systems and biomedical applications based on NIR-II imaging, such as multimodal imaging, photothermal and photodynamic therapy, guidance for intraoperative surgery, and drug delivery.

Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)-assisted conversion of glucose into gluconic acid and toxic H O , a novel treatment paradigm of starving-like therapy is developed for significant tumor-killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H O can oxidize l-Arginine (l-Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co-delivery of GOx and l-Arg, a novel glucose-responsive nanomedicine (l-Arg-HMON-GOx) has been for the first time constructed for synergistic cancer starving-like/gas therapy without the need of external excitation, which yields a remarkable H O -NO cooperative anticancer effect with minimal adverse effect.

Nonlayered materials are constructed with chemical covalent bonds in all three dimensions, distinct from layered materials, which contain evident structural differences in the horizontal and vertical directions. As a consequence, liquid‐phase exfoliation (LPE), a widely explored technique to obtain 2D layered nanoarchitectures, has not yet been fully characterized for the realization of 2D nonlayered nanostructures. Herein, by virtue of a typical chain‐like structure of crystalline bulk Te with strong TeTe covalent bonds in intrachains and weak Van der Waals forces in interchains, ultrathin 2D nonlayered Te nanosheets are realized by means of an LPE method. The resultant 2D Te nanosheets possess a broad lateral dimension ranging from 41.5 to 177.5 nm and a thickness ranging from 5.1 to 6.4 nm, and its photoresponse properties are evaluated using photoelectrochemical measurements. The 2D Te nanosheets exhibit excellent photoresponse behaviors from the UV to the visible regime in association with strong time and cycle stability for the on/off switching behaviors. The fabrication approach of 2D Te nanosheets would arouse interest in exfoliating other nonlayered 2D materials, which would expand the family of 2D materials.

Nanocarbons with different dimensions (e.g., 0D fullerenes and carbon nanodots, 1D carbon nanotubes and graphene nanoribbons, 2D graphene and graphene oxides, and 3D nanodiamonds) have attracted enormous interest for applications ranging from electronics, optoelectronics, and photovoltaics to sensing, bioimaging, and therapeutics due to their unique physical and chemical properties. Among them, nanocarbon-based theranostics (i.e., therapeutics and diagnostics) is one of the most intensively studied applications, as these nanocarbon materials serve as excellent biosensors, versatile drug/gene carriers for specific targeting in vivo, effective photothermal nanoagents for cancer therapy, and promising fluorescent nanolabels for cell and tissue imaging. This review provides a systematic overview of the latest theranostic applications of nanocarbon materials with a comprehensive comparison of the characteristics of different nanocarbon materials and their influences on theranostic applications. We first introduce the different carbon allotropes that can be used for theranostic applications with their respective preparation and surface functionalization approaches as well as their physical and chemical properties. Theranostic applications are described separately for both in vitro and in vivo systems by highlighting the protocols and the studied biosystems, followed by the toxicity and biodegradability implications. Finally, this review outlines the design considerations for nanocarbon materials as the key unifying themes that will serve as a foundational first principle for researchers to study, investigate, and generate effective, biocompatible, and nontoxic nanocarbon materials-based models for cancer theranostics applications. Finally, we summarize the review with an outlook on the challenges and novel theranostic protocols using nanocarbon materials for hard-to-treat cancers and other diseases. This review intends to present a comprehensive guideline for researchers in nanotechnology and biomedicine on the selection strategy of nanocarbon materials according to their specific requirements. CONTENTSRelated Molecules by Different Nano-54 carbon Materials W 55 2.2. Nanocarbons for in Vitro Bioimaging AD 56 2.2.1. In Vitro Imaging by Graphene AD 57 2.2.2. In Vitro Imaging by Carbon Nanotubes AF 58 2.2.3. In Vitro Imaging by Fullerenes AH 59 2.2.4. In Vitro Imaging by Carbon Nanohorns AI 60 2.2.5. In Vitro Imaging by Nanodiamonds AJ

In this work, we constructed a Collagen I-Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).M etastasis is a lethal milestone in cancer: Cells escape from the confinement of primary tumor sites (intravasation), invade tissues as well as the lymphatic and vascular systems, and finally colonize (extravasation) distant sites. It has been estimated that less than 1% of tumor cells undergo this process, but metastasis contributes to more than 90% of cancerrelated deaths (1, 2). Metastasis involves both genetic and epigenetic alternation of tumor cells, as well as external biochemical and biophysical microenvironments (3-5). Pathology studies suggest that metastatic tumor cells exhibit highly branched morphologies and distinct aligned registration with aligned extracellular matrix (ECM) during metastatic tumor progression (4, 5).We address three important questions concerning metastasis. (i) Can we build in vitro complex ECM structures with heterogeneously oriented collagen fibers and basement membrane components to mimic the cancer cell intravasation process? (ii) How does aligned collagen influence cell intravasation into/ through the basement membrane before entering vessels? (iii) After cell detachment from the primary tumor site, how does a heterogeneous ECM with a varying degree of local fiber alignment influence cell intravasation and subsequent penetration into the basement membrane during their intravasation process? The major obstacle to addressing these questions is the difficulty in constructing both an in vitro 3D microenvironment to mimic the above process and flexible controls of the environmental parameters, such as fiber orientations in a complex collagen/Matrigel composite, nutrition, oxygen, drug concentrations, etc.In breast cancer metastasis, cancer cells are believed to reorganize and progress through the interstitial ECM matrix, break through the basement membrane, and enter blood vessels or lymphatic capillaries (6-10). Fig. 1C presents a schematic illustration of the intravasation process in metastasis. Tumor-associated collagen signatures (TACS), basically environmentally elevated collagen density and collagen fiber reorganization, are used to stage mammary carcinoma tumor progression levels (6, 11-13). Fig. 1 presents hematoxylin/eosin (H&E)-stained biopsy slices of breast cancer imaged by second harmonic generation (SHG) under a two-photon confocal microscopy (A1R MP; Nikon) (detailed information provided in SI Appendix, SI Text) (6, 14, 15). Fig. 1 A, 1-3 shows the stained human invasive ductal carcinoma tumor at grade I. In the enlarged figures (Fig. 1 A, 2 and 3), the cells have well-defined bord...