Near-infrared II plasmonic porous cubic nanoshells for in vivo noninvasive SERS visualization of sub-millimeter microtumors.

In vivo surface-enhanced Raman scattering (SERS) imaging allows non-invasive visualization of tumors for intraoperative guidance and clinical diagnostics. However, the in vivo utility of SERS is greatly hampered by the strong optical scattering and autofluorescence background of biological tissues and the lack of highly active plasmonic nanostructures. Herein, we report a class of porous nanostructures comprising a cubic AuAg alloy nanoshell and numerous nanopores. Such porous nanostructures exhibit excellent near-infrared II plasmonic properties tunable in a broad spectral range by varying the pore features while maintaining a small dimension. We demonstrate their exceptional near-infrared II SERS performance varying with the porous properties. Additionally, near-infrared II SERS probes created with porous cubic AuAg nanoshells are demonstrated with remarkable capability for in vivo visualization of sub-millimeter microtumors in a living mouse model. Our near-infrared II SERS probes hold great potentials for precise demarcation of tumor margins and identification of microscopic tumors.

Biodegradable Amorphous Copper Iron Tellurite Promoting the Utilization of Fenton-Like Ions for Efficient Synergistic Cancer Theranostics.

The major hurdles of chemodynamic therapy (CDT) are nondegradability and low-efficiency utilization of chemodynamic agents, and intracellular glutathione (GSH)-induced rapid scavenging of hydroxyl radicals (•OH). Here, a biodegradable a-CFT@IP6@BSA agent is reported for efficient cancer therapy by encapsulating amorphous copper iron tellurite nanoparticles (a-CFT NPs) into inositol hexaphosphate (IP6) and bovine serum albumin (BSA). The biggest merits of this agent are the GSH responsive degradation and amorphous structure, allowing the tumor-specific release of plenty of Cu+ ions and their high-efficiency utilization for •OH production via the Fenton-like reaction. Besides, the released Cu+ ions can deplete the intracellular GSH and thereby protect •OH from scavenging, greatly improving the CDT efficiency. Further, it is found that the a-CFT@IP6@BSA NP treatment down-regulates the levels of glutathione peroxidase 4 and BCL-2, indicating GSH depletion-associated ferroptosis and IP6-induced apoptotic death of cancer cells. Utilizing the T1/T2 dual-modal magnetic resonance imaging capability, the a-CFT@IP6@BSA NPs are demonstrated with excellent in vivo anticancer efficiency and have great potential for imaging-guided cancer treatment.

Near-Infrared II Plasmonic Phototheranostics with Glutathione Depletion for Multimodal Imaging-Guided Hypoxia-Tolerant Chemodynamic-Photocatalytic-Photothermal Cancer Therapy Triggered by a Single Laser.

Tumor microenvironment (TME)-activatable phototheranostics is highly desirable in cancer management but still remains challenging for clinical applications owing to the lack of multifunctional theranostic agents and the limited tissue penetration depth. Reported here is an "all-in-one" phototheranostic platform based on near-infrared II (NIR-II) dual-plasmonic Au@Cu2-x Se core-shell nanocrystals (dpGCS NCs) for combined photoacoustic (PA)/photothermal (PT) imaging-guided chemodynamic therapy (CDT)/photocatalytic therapy (PCT)/photothermal therapy (PTT) all triggered by a single NIR-II laser. The dpGCS NCs feature excellent NIR-II plasmonic and PT properties, which guarantee their capabilities of NIR-II PA and PT imaging for real-time visual observation of tumor size and location during cancer treatment. Additionally, the TME-activated in situ •OH production via dpGCS NC-catalyzed Fenton-like reaction is further enhanced by the NIR-II irradiation, while photoexcited plasmonic hole-induced formation of extra •OH is also evidenced for PCT. Both in vitro and in vivo experiments confirm remarkable therapeutic efficacy of the present phototheranostic platform under NIR-II laser through the CDT/PCT/PTT trimodal combination therapy, achieving complete inhibition of tumor growth in tumor-bearing mice after administration of dpGCS NCs plus a single NIR-II laser irradiation. This work provides a distinctive paradigm for the development of NIR-II phototheranostic platforms for imaging-guided cancer therapy using a single laser.

Rationally designed dual-plasmonic gold nanorod@cuprous selenide hybrid heterostructures by regioselective overgrowth for in vivo photothermal tumor ablation in the second near-infrared biowindow.

NIR-II plasmonic materials offer multiple functionalities for in vivo biomedical applications, such as photothermal tumor ablation, surface-enhanced Raman scattering biosensing, photoacoustic imaging, and drug carriers. However, integration of noble metals and plasmonic semiconductors is greatly challenging because of the large lattice-mismatch. This study reports the regioselective overgrowth of Cu2-xSe on gold nanorods (GNRs) for preparation of dual-plasmonic GNR@Cu2-xSe hybrid heterostructures with tunable NIR-II plasmon resonance absorption for in vivo photothermal tumor ablation. Methods: The regioselective deposition of amorphous Se and its subsequent conversion into Cu2-xSe on the GNRs are performed by altering capping agents to produce the GNR@Cu2-xSe heterostructures of various morphologies. Their photothermal performances for NIR-II photothermal tumor ablation are evaluated both in vitro and in vivo. Results: We find that the lateral one- and two-side deposition, conformal core-shell coating and island growth of Cu2-xSe on the GNRs can be achieved using different capping agents. The Cu2-xSe domain size in these hybrids can be effectively adjusted by the SeO2 concentration, thereby tuning the NIR-II plasmon bands. A photothermal conversion efficiency up to 58-85% and superior photostability of these dual-plasmonic hybrids can be achieved under the NIR-II laser. Results also show that the photothermal conversion efficiency is dependent on the proportion of optical absorption converted into heat; however, the temperature rise is tightly related to the concentration of their constituents. The excellent NIR-II photothermal effect is further verified in the following in vitro and in vivo experiments. Conclusions: This study achieves one-side or two-side deposition, conformal core-shell coating, and island deposition of Cu2-xSe on GNRs for GNR@Cu2-xSe heterostructures with NIR-II plasmonic absorption, and further demonstrates their excellent NIR-II photothermal tumor ablation in vivo. This study provides a promising strategy for the rational design of NIR-II dual-plasmonic heterostructures and highlights their therapeutic in vivo potential.

A graphene oxide-gold nanostar hybrid based-paper biosensor for label-free SERS detection of serum bilirubin for diagnosis of jaundice.

We report a paper-based surface-enhanced Raman spectroscopy (SERS) biosensor integrating the enrichment capability, namely enPSERS biosensor, for the sensitive, label-free detection of free bilirubin in blood serum for the accurate diagnosis of jaundice and its related diseases. This biosensor comprises multifunctional graphene oxide-plasmonic gold nanostar (GO-GNS) hybrids decorated on the filter paper, which integrates the high sensitivity of SERS detection, enrichment for serum bilirubin and fluorescence superquenching capability of GO-GNS hybrids for sensitive detection of serum bilirubin. The study of adsorption kinetics reveals that both electrostatic and π-π interactions between the GO-GNS hybrids and targets are responsible for the enrichment of bilirubin, and the adsorption process follows the pseudo-second-order kinetic model. The results of SERS detection of bilirubin in blood serum show two differential linear response ranges from 5.0 to 150 µM and 150-500 µM with the detection limit as low as 0.436 µM. The comparison of the results obtained from our present enPSERS biosensor with the commercial diazo reaction method for determination of free bilirubin in blood serum reveals the clinical effectiveness and suitability of the developed paper-based SERS biosensor. We believe that this sensitive and label-free SERS biosensor holds considerable promise for clinical translation in accurate diagnosis of jaundice.

Combining Experiments and Theoretical Modeling To Interrogate the Anisotropic Growth and Structure-Plasmonic Property Relationships of Gold Nanostars.

We present a combined strategy of experiments and theoretical modeling for understanding the evolution of the morphology and plasmonic properties of gold nanostars (GNSs) in the seed-mediated synthesis by changing the poly(vinylpyrrolidone) (PVP) molecular weight, PVP concentration, and synthesis temperature. A dramatic change of the morphology of GNSs as a function of these synthesis parameters is observed that is related to variations of the plasmonic properties and thus surface-enhanced Raman spectroscopy (SERS) enhancement. We observe the favorable growth of anisotropic GNS structures with sharp protruding tips using PVP of low molecular weight and of rounded GNSs with short protruding tips using PVP of high molecular weight. The PVP concentration has less influence on the core size than on the tip length of GNSs. The high synthesis temperature causes the rounding of the GNS structure. Finite-difference time-domain (FDTD) simulations reveal a remarkable correlation of the GNS morphology with the plasmonic properties as well as the SERS enhancement. The maximum local electric field enhancement occurs at the apex of the sharp protruding tips of the GNSs. The weak plasmonic coupling is observed between the protruding tips of GNSs because of their large separation distance, and increasing the number of protruding tips beyond two only increases the extinction cross section without further red-shifting the plasmon peak. A resonance overlap of the plasmon band with the incident laser wavelength is responsible for the morphology-dependent plasmonic properties and SERS enhancement. The present work demonstrates that a mechanistic understanding of the structural evolution of GNSs along with their morphology-plasmonic property correlation can be achieved through the combination of experimental investigations and FDTD-based theoretical modeling.

In Situ Raman Spectroscopic Studies of Thermal Stability of All-Inorganic Cesium Lead Halide (CsPbX3, X = Cl, Br, I) Perovskite Nanocrystals.

Thermal degradation becomes the main obstacle for industrial applications of all-inorganic cesium lead halide (CsPbX3, X = Cl, Br, I) perovskite optoelectronic devices. A complete understanding of thermal degradation of CsPbX3 perovskites is required but greatly challenging for achieving optoelectronic devices with long-term stability, particularly under extreme settings. Herein, we present an in situ spectroscopic study of thermal stability of CsPbX3 nanocrystals between the cryogenic temperature and high temperature. The low-frequency Raman signatures of CsPbX3 nanocrystals dramatically evolve but differentiate from the halogen atoms at elevated temperatures, acting as potent indicators of their crystalline structures and phase transitions. The merging of doublet Raman bands of CsPbX3 nanocrystals indicates their high-temperature phase transitions. CsPbX3 (X = Br, I) nanocrystals undergo a state of high degree of disorder with featureless Raman spectra before being thermally decomposed. Such understanding is of particular importance for future design and optimization of high-performance CsPbX3 perovskite devices with long-term stability under extreme settings.

Surface-enhanced Raman spectroscopy (SERS) nanoprobes for ratiometric detection of cancer cells.

We report a ratiometric strategy for detection of different types of breast cancer cells by surface-enhanced Raman spectroscopy (SERS), which simultaneously quantifies the levels of dual biomarkers distinctly expressed on cancer cells to consequently achieve their expression ratio. Two SERS nanoprobes that are encoded with distinct SERS signatures are conjugated with urokinase plasminogen activation receptor (uPAR)- and epidermal growth factor receptor (EGFR)-targeting peptides. The SERS imaging of single live cells can accurately quantify the cellular biomarker expression difference from the SERS intensity ratio and is further employed for cancer cell screening. The results show that MDA-MB-231 and MCF-7 exhibit distinct expression of the uPAR and EGFR and they can be respectively discriminated by the intensity ratio of SERS signals from uPAR- and EGFR-targeting SERS nanoprobes. The ratiometric strategy permits background-free SERS detection of cancer cells and dramatically improves the signal-to-noise ratio of targeted cellular SERS imaging, thus enabling accurate cancer cell screening without the need for additional references. It is believed that the present ratiometric method should be a promising avenue for breast cancer diagnostics and screening, which can be easily extended for detection of other cancer cell types.