Some infectious or malignant diseases such as cancers are seriously threatening the health of human beings all over the world. The commonly used antibiotic therapy cannot effectively treat these diseases within a short time, and also bring about adverse effects such as drug resistance and immune system damage during long-term systemic treatment. Phototherapy is an emerging antibiotic-free strategy to treat these diseases. Upon light irradiation, phototherapeutic agents can generate cytotoxic reactive oxygen species (ROS) or induce a temperature increase, which leads to the death of targeted cells. These two kinds of killing strategies are referred to as photodynamic therapy (PDT) and photothermal therapy (PTT), respectively. So far, many photo-responsive agents have been developed. Among them, the metal-organic framework (MOF) is becoming one of the most promising photo-responsive materials because its structure and chemical compositions can be easily modulated to achieve specific functions. MOFs can have intrinsic photodynamic or photothermal ability under the rational design of MOF construction, or serve as the carrier of therapeutic agents, owing to its tunable porosity. MOFs also provide feasibility for various combined therapies and targeting methods, which improves the efficiency of phototherapy. In this review, we firstly investigated the principles of phototherapy, and comprehensively summarized recent advances of MOF in PDT, PTT and synergistic therapy, from construction to modification. We expect that our demonstration will shed light on the future development of this field, and bring it one step closer to clinical trials.

The recent progress on metal-organic frameworks for phototherapy.

Reactive oxygen species (ROS) play an essential role in physiological and pathological processes. Studies on the regulation of ROS for disease treatments have caused wide concern, mainly involving the topics in ROS-regulating therapy such as antioxidant therapy triggered by ROS scavengers and ROS-induced toxic therapy mediated by ROS-elevation agents. Benefiting from the remarkable advances of nanotechnology, a large number of nanomaterials with the ROS-regulating ability are developed to seek new and effective ROS-related nanotherapeutic modalities or nanomedicines. Although considerable achievements have been made in ROS-based nanomedicines for disease treatments, some fundamental but key questions such as the rational design principle for ROS-related nanomaterials are held in low regard. Here, the design principle can serve as the initial framework for scientists and technicians to design and optimize the ROS-regulating nanomedicines, thereby minimizing the gap of nanomedicines for biomedical application during the design stage. Herein, an overview of the current progress of ROS-associated nanomedicines in disease treatments is summarized. And then, by particularly addressing these known strategies in ROS-associated therapy, several fundamental and key principles for the design of ROS-associated nanomedicines are presented. Finally, future perspectives are also discussed in depth for the development of ROS-associated nanomedicines.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202002797

Reactive Oxygen Species-Regulating Strategies Based on Nanomaterials for Disease Treatment.

In recent years, bioanalytical surface-enhanced Raman spectroscopy (SERS) has blossomed into a fast-growing research area. Owing to its high sensitivity and outstanding multiplexing ability, SERS is an effective analytical technique that has excellent potential in bioanalysis and diagnosis, as demonstrated by its increasing applications in vivo. SERS allows the rapid detection of molecular species based on direct and indirect strategies. Because it benefits from the tunable surface properties of nanostructures, it finds a broad range of applications with clinical relevance, such as biological sensing, drug delivery and live cell imaging assays. Of particular interest are early-stage-cancer detection and the fast detection of pathogens. Here, we present a comprehensive survey of SERS-based assays, from basic considerations to bioanalytical applications. Our main focus is on SERS-based pathogen detection methods as point-of-care solutions for early bacterial infection detection and chronic disease diagnosis. Additionally, various promising in vivo applications of SERS are surveyed. Furthermore, we provide a brief outlook of recent endeavours and we discuss future prospects and limitations for SERS, as a reliable approach for rapid and sensitive bioanalysis and diagnosis.

/pdf/surface-enhanced-raman-spectroscopy-for-bioanalysis-and-5fesoo09gf.pdf

Surface-enhanced Raman spectroscopy for bioanalysis and diagnosis

Multifunctional Prussian blue-based nanomaterials: Preparation, modification, and theranostic applications

A biodegradable "Nano-donut" for magnetic resonance imaging and enhanced chemo/photothermal/chemodynamic therapy through responsive catalysis in tumor microenvironment.

Surface-enhanced Raman scattering (SERS) and magnetic resonance imaging (MRI)-guided phototherapy are new breakthroughs in cancer therapeutics due to their complementary advantages, such as enhanced imaging spatial resolution and depth. Herein, we synthesized monodispersed Prussian blue-encapsulated gold nanoparticles (Au@PB NPs), in which the plasmonic gold core plus coordination polymer of cyanide (C[triple bond, length as m-dash]N) and iron ions coincidently become a superexcellent contrast agent for both MRI and zero-background SERS imaging. PB, as a signal source for MR and SERS, can be easily assembled onto single Au NPs, of which iron ions possess high relaxation efficiency for in vivo MRI, e.g., the longitudinal and transversal relaxation efficiency values are 0.86 mM-1 s-1 (r1) and 5.42 mM-1 s-1 (r2), respectively. Furthermore, with the help of the plasmonic enhancement of the gold core, the C[triple bond, length as m-dash]N groups exhibit a specific, strong, and stable (3S) SERS emission in the Raman-silent region (1800-2800 cm-1), allowing accurate in vivo imaging at the single or even subcellular level. More importantly, PB has remarkable absorption properties in the near infrared region, and can be used as a photosensitizer for photothermal (PT) and photodynamic (PD) therapy simultaneously. Hence, the ideal integration of a plasmonic Au core and PB shell into a single monodispersed MR-guided NP, with zero-background SERS signals, is an important candidate for both tumor navigation and in situ PT/PD treatment guided by SERS/MR dual-mode imaging.

Monodispersed plasmonic Prussian blue nanoparticles for zero-background SERS/MRI-guided phototherapy

Although homogeneous detection of some biomolecules has been of great significance in clinical assay, it faces great challenges in achieving precise in situ imaging of biomolecules. In addition, nonspecific adsorption between probes and biomolecules and low sensitivity are still unfathomed problems. Herein, we developed a promoted "Click" surface enhanced Raman scattering (SERS) strategy for realizing highly selective homogeneous detection of biomolecules by simultaneous dual enhanced SERS emissions, obtaining mutually confirmed logical judgment. Taking caspase-3 as one of the biotargets, we have realized highly selective homogeneous detection of caspase-3 using this strategy, and precise intracellular imaging of caspase-3 can be in situ monitored in living cells or during cell apoptosis. In detail, polyA-DNA and the Asp-Glu-Val-Asp (DEVD)-containing peptide sequence were modified into alkyne and nitrile-coded Au nanoparticles (NPs). During the cell apoptosis process, the generated caspase-3 would lead to the cleavage of the tetra-peptide sequence DEVD, thereby removing the negative protection part from the peptide on Au NPs. Interestingly, two different triple bond-labeled Au NPs can be connected together through DNA hybridization to form SERS "hotspot", resulting in simultaneously enlarged triple bond Raman signals. Moreover, we found that the SERS intensity was positively related with caspase-3 concentration, which has a wide linear range (0.1 ng/mL to 10 μg/mL) and low detection limit (7.18 × 10-2 ng/mL). Remarkably, these simultaneously enlarged signals by "Click" SERS could be used for more precise imaging of caspase-3, providing mutually confirmed logical judgment based on two spliced SERS emissions, especially for their relative intensity.

Promoted "Click" SERS Detection for Precise Intracellular Imaging of Caspase-3.

Stimulated Raman scattering (SRS) microscopy in combination with innovative tagging strategies offers great potential as a universal high-throughput biomedical imaging tool. Here, we report rationally tailored small molecular monomers containing triple-bond units with large Raman scattering cross-sections, which can be polymerized at the nanoscale for enhancement of SRS contrast with smaller but brighter optical nanotags with artificial fingerprint output. From this, a class of triple-bond rich polymer nanoparticles (NPs) was engineered by regulating the relative dosages of three chemically different triple-bond monomers in co-polymerization. The bonding strategy allowed for 15 spectrally distinguishable triple-bond combinations. These accurately structured nano molecular aggregates, rather than long-chain macromolecules, could establish a universal method for generating small-sized biological SRS imaging tags with high sensitivity for high-throughput multi-color biomedical imaging.

Precise Encoding of Triple-Bond Raman Scattering of Single Polymer Nanoparticles for Multiplexed Imaging Application

The reliability and reproducibility of surface-enhanced Raman scattering (SERS) technology is still a great challenge in bio-related analysis. Prussian blue (PB)-based SERS tags have attracted increasing interest for improving these deficiencies due to its unique Raman band (near 2156 cm−1) in the Raman-silent region, providing zero-background bio-Raman labels without interference from endogenous biomolecules. Moreover, the stable PB shell consisting of multiple layers of CN− reporters ensure a stable and strong Raman signal output, avoiding the desorption of the Raman reporter from the plasmonic region by the competitive adsorption of the analyte. More importantly, they possess outstanding multiplexing potential in biological analysis owing to the adjustable Raman shift with unique narrow spectral widths. Despite more attention having been attracted to the structure and preparation of PB-based SERS tags for their better biological applications over the past five years, there is still a great challenge for SERS suitable for applications in the actual environment. The biological applications of PB-based SERS tags are comprehensively recounted in this minireview, mainly focusing on quantification analysis, multiple-spectral analysis and cell-imaging joint phototherapy. The prospects of PB-based SERS tags in clinical diagnosis and treatment are also discussed. This review aims to draw attention to the importance of SERS tags and provide a reference for the design and application of PB-based SERS tags in future bio-applications.

/pdf/recent-advances-in-plasmonic-prussian-blue-based-sers-39a6m4ratt.pdf

Recent advances in plasmonic Prussian blue-based SERS nanotags for biological application

Rational synthesis of Three-Layered plasmonic nanocomposites of copper Sulfide/Gold/Zinc-Doped Prussian blue analogues for improved photothermal disinfection and wound healing

Wei Zhu

Papers

Monodispersed plasmonic Prussian blue nanoparticles for zero-background SERS/MRI-guided phototherapy

Promoted "Click" SERS Detection for Precise Intracellular Imaging of Caspase-3.

Precise Encoding of Triple-Bond Raman Scattering of Single Polymer Nanoparticles for Multiplexed Imaging Application

Recent advances in plasmonic Prussian blue-based SERS nanotags for biological application

Rational synthesis of Three-Layered plasmonic nanocomposites of copper Sulfide/Gold/Zinc-Doped Prussian blue analogues for improved photothermal disinfection and wound healing