NIR-II nanoprobes for investigating the glymphatic system function under anesthesia and stroke injury.

The glymphatic system plays an important role in the transportation of cerebrospinal fluid (CSF) and the clearance of metabolite waste in brain. However, current imaging modalities for studying the glymphatic system are limited. Herein, we apply NIR-II nanoprobes with non-invasive and high-contrast advantages to comprehensively explore the function of glymphatic system in mice under anesthesia and cerebral ischemia-reperfusion injury conditions. Our results show that the supplement drug dexmedetomidine (Dex) enhances CSF influx in the brain, decreases its outflow to mandibular lymph nodes, and leads to significant differences in CSF accumulation pattern in the spine compared to isoflurane (ISO) alone, while both ISO and Dex do not affect the clearance of tracer-filled CSF into blood circulation. Notably, we confirm the compromised glymphatic function after cerebral ischemia-reperfusion injury, leading to impaired glymphatic influx and reduced glymphatic efflux. This technique has great potential to elucidate the underlying mechanisms between the glymphatic system and central nervous system diseases.

NIR-II Imaging-Guided Mitochondrial-Targeting Organic Nanoparticles for Multimodal Synergistic Tumor Therapy.

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.

Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors.

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv ß3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES-GON-PAA@RGD2 with remarkable relaxivities is a promising and powerful T1 -weighted MRI contrast agent.

Cellulose Nanocrystal Films with NIR-II Circularly Polarized Light for Cancer Detection Applications.

Near-infrared circularly polarized light is attractive for wide-ranging applications. However, high-performance near-infrared circularly polarized light is challenging to realize. Here, we show that left-handed chiral photonic cellulose nanocrystal (CNC) films produced from ultrasonicated suspensions enable right-handed circularly polarized luminescence with a dissymmetry factor of -0.330 in the second near-infrared window (NIR-II). We present a theoretical analysis of the adverse effect of structural defects and luminescence intensity heterogeneity on the right-handed circularly polarized luminescence glum inside the bandgap and the occurrence of left-handed circularly polarized luminescence at the band edges. We demonstrate the potential of the chiral photonic CNC films with NIR-II circularly polarized light for cancer cell discrimination. The present work identifies key scientific questions in CNC-based circularly polarized luminescence materials research.

Molecular imprinting of glycoproteins: From preparation to cancer theranostics.

Glycoprotein imprinted polymers have rapidly grown as excellent receptors for cancer targeting, diagnostics, inhibition, and nanomedicines as they specifically target glycans and glycosites overexpressed in various tumors. Compared to natural antibodies, they are easy to synthesize, stable, and cost-efficient. Currently, no study specifically discusses glycoproteins imprinting strategies for cancer theranostics. In this review, firstly we explored various factors involved in designing and synthesis of glycoprotein imprinted materials, including, the characteristics and choice of monomers for imprinting, types of templates and their interactions involved, and the imprinting methods. Secondly, the integration of these MIPs with different probes that have been applied for in vitro and in vivo targeting for cancer diagnostics including biosensing and bioimaging, and image-guided therapeutic applications as nanomedicines. These Glycoprotein imprinted polymers have been found to specifically target the glycoprotein biomarkers and glycosylated cell receptors overexpressed in different cancers and have been reported as excellent diagnostic tools. As nanomedicines, they have been potentially employed in various modes of cancer therapy such as targeted drug delivery, photodynamic therapy, photothermal therapy, and nanoMIPs themselves as therapeutics for locally killing tumor cells. Although the research is still in its early stages and no real-world clinical trials on humans have been conducted, nanoMIPs have a promising future in this field. We believe these findings will pave the way for MIPs in advanced diagnostics, antibody treatment, and immunotherapy as future nanomedicine for real-world cancer theranostics.

Near-Infrared Carbonized Polymer Dots for NIR-II Bioimaging.

Carbon dots (CDs) or carbonized polymer dots (CPDs) are an emerging class of optical materials that have exceptional applications in optoelectronic devices, catalysis, detection, and bioimaging. Although cell studies of CPDs have produced impressive results, in vivo imaging requires available CPDs to fluoresce in the near-infrared-II (NIR-II) window (1000-1700 nm). Here, a two-step bottom-up strategy is developed to synthesize NIR-CPDs that provide bright emissions in both NIR-I and NIR-II transparent imaging windows. The designed strategy includes a hydrothermal reaction to form a stable carbon core with aldehyde groups, followed by the Knoevenagel reaction to tether the molecular emission centers. This procedure is labor-saving, cost-efficient, and produces a high yield. The NIR-CPDs enable high-performance NIR-II angiography and real-time imaging of the disease degree of colitis noninvasively. This technology may therefore provide a next-generation synthesis strategy for CPDs with rational molecular engineering that can accurately tune the absorption/emission properties of NIR-emissive CPDs.

Fabrication of silicon/polymer composite nanopost arrays and their sensing applications.

A novel technique is reported for fabricating silicon/polymer composite nanopost arrays by combining colloidal lithography and surface-initiated atom-transfer radical polymerization. The composite nanopost arrays possess a core/shell nanoarchitecture, with shells of poly(2-hydroxyethyl methacrylate) and cores of silicon nanoposts. The polymer brush possesses quasi-3D homogeneous nanoarchitectures due to the controllable polymerization process using the surface-initiated atom-transfer radical polymerization technique. The composite nanopost arrays are durable due to the particular nanoarchitectures. The backbone templates of the composites are silicon nanopost arrays directly etched from silicon substrates, and the polymer shell is covalently grafted from the arrays. The composite nanopost arrays exhibit vivid colors. Moreover, the colors of the composite nanopost arrays can be tuned from green to red by changing the thickness of fi lm. Specifically, the composite nanopost arrays can be used as sensors to rapidly detect water vapors with high stability and reproducibility. Many different functional surfaces could be prepared through this technique using other functional monomers.

Ascorbic Acid-PEI Carbon Dots with Osteogenic Effects as miR-2861 Carriers to Effectively Enhance Bone Regeneration.

Nucleic acid transfer has shown significant potential in the treatment of bone damage because of its long lasting local effect and lower cost. Nonviral vectors, such as nanomaterials, with higher biocompatibility are increasedly applied in the study of bone defect repair. Carbon dots with various reactive groups on the surface not only provide a unique surface to carry therapeutic genes, but also some carbon dots have been reported to promote osteogenic differentiation. The bone regeneration effect of carbon dots in vivo, however, is rarely investigated. MiR-2861 has revealed osteogenic differentiation effects. In the current study, we created ascorbic acid-PEI carbon dots (CD), which were able to carry miR-2861, by the microwave-assisted pyrolysis method. Results demonstrated that CD had excellent fluorescence stability leading to good fluorescence imaging in vitro and in vivo. CD was efficiently internalized into bone marrow stromal cells (BMSCs) through the clathrin-mediated endocytosis pathway and distributed in the mitochondria, endoplasmic reticulum, lysosome, and nucleus. Results from alkaline phosphatase staining, alizarin red staining, and reverse transcription real-time PCR (RT-QPCR) showed that our CD indeed had osteogenic effects in vitro. Flow cytometry data indicated that CD could efficiently deliver miR-2861 into BMSCs in vitro, and CD carrying miR-2861 (CD@miR) had the strongest osteogenic effects. Analyses of hematology, serum biochemistry, and histology showed that CD and CD@miR did not have cytotoxicity and had higher biocompatibility in vivo. Most interestingly, CD and miR-2861 in the CD@miR could act synergistically to promote osteogenic differentiation in vitro and new bone regeneration in vivo remarkably. Our results clearly indicate that the osteogenic CD delivering osteogenic therapeutic gene, miR-2861, can obtain much stronger bone regeneration ability, suggesting that our CD has great potential in future clinical application.

Deep Red Emissive Carbonized Polymer Dots with Unprecedented Narrow Full Width at Half Maximum.

Development of high-performance carbon dots (CDs) with emission wavelength longer than 660 nm (deep red emission) is critical in deep-tissue bioimaging, yet it is still a major challenge to obtain CDs with both narrow full width at half maximum (FWHM) and high deep red/near-infrared emission yield. Here, deep red emissive carbonized polymer dots (CPDs) with unprecedented FWHM of 20 nm are synthesized. The purified CPDs in dimethyl sulfoxide (DMSO) solution possess quantum yield (QY) as high as 59% under 413 nm excitation, as well as recorded QY of 31% under 660 nm excitation in the deep red fluorescent window. Detailed characterizations identify that CPDs have unique polymer characteristics, consisting of carbon cores and the shells of polymer chains, and π conjugated system formed with N heterocycles and aromatic rings governs the single photoluminescence (PL) center, which is responsible for high QY in deep red emissive CPDs with narrow FWHM. The CPDs exhibit strong absorption and emission in the deep red light region, low toxicity, and good biocompatibility, making them an efficient probe for both one-photon and two-photon bioimaging. CPDs are rapidly excreted via the kidney system and hepatobiliary system.

Carbon dots-fed Shewanella oneidensis MR-1 for bioelectricity enhancement.

Bioelectricity generation, by Shewanella oneidensis (S. oneidensis) MR-1, has become particularly alluring, thanks to its extraordinary prospects for energy production, pollution treatment, and biosynthesis. Attempts to improve its technological output by modification of S. oneidensis MR-1 remains complicated, expensive and inefficient. Herein, we report on the augmentation of S. oneidensis MR-1 with carbon dots (CDs). The CDs-fed cells show accelerated extracellular electron transfer and metabolic rate, with increased intracellular charge, higher adenosine triphosphate level, quicker substrate consumption and more abundant extracellular secretion. Meanwhile, the CDs promote cellular adhesion, electronegativity, and biofilm formation. In bioelectrical systems the CDs-fed cells increase the maximum current value, 7.34 fold, and power output, 6.46 fold. The enhancement efficacy is found to be strongly dependent on the surface charge of the CDs. This work demonstrates a simple, cost-effective and efficient route to improve bioelectricity generation of S. oneidensis MR-1, holding promise in all relevant technologies.

Multiplexed NIR-II Probes for Lymph Node-Invaded Cancer Detection and Imaging-Guided Surgery.

Tumor-lymph node (LN) metastasis is the dominant prognostic factor for tumor staging and therapeutic decision-making. However, concurrently visualizing metastasis and performing imaging-guided lymph node surgery is challenging. Here, a multiplexed-near-infrared-II (NIR-II) in vivo imaging system using nonoverlapping NIR-II probes with markedly suppressed photon scattering and zero-autofluorescence is reported, which enables visualization of the metastatic tumor and the tumor metastatic proximal LNs resection. A bright and tumor-seeking donor-acceptor-donor (D-A-D) dye, IR-FD, is screened for primary/metastatic tumor imaging in the NIR-IIa (1100-1300 nm) window. This optimized D-A-D dye exhibits greatly improved quantum yield of organic D-A-D fluorophores in aqueous solutions (≈6.0%) and good in vivo performance. Ultrabright PbS/CdS core/shell quantum dots (QDs) with dense polymer coating are used to visualize cancer-invaded sentinel LNs in the NIR-IIb (>1500 nm) window. Compared to clinically used indocyanine green, the QDs show superior brightness and photostability (no obvious bleaching even after continuous laser irradiation for 5 h); thus, only a picomolar dose is required for sentinel LNs detection. This combination of dual-NIR-II image-guided surgery can be performed under bright light, adding to its convenience and appeal in clinical use.

Carbonized Polymer Dots: A Brand New Perspective to Recognize Luminescent Carbon-Based Nanomaterials.

Carbon dots (CDs), as emerging luminescent nanomaterials, possess excellent but complex properties, bringing about extensive attention and a lot of controversy. In this Perspective, we put forward the concept of "carbonized polymer dots" and emphasize the important role of polymerization and carbonization during the formation of CDs. We explore the common characters and clarify the complicated relationship of CDs, based on the reasonable classification of graphene quantum dots, carbon quantum dots, and carbonized polymer dots. Moreover, different perspectives are provided for comprehensive analysis about the essence of CDs, including quantum dots, molecules, and polymers. The photoluminescence mechanism has been classified into molecule state, carbon core state, surface/edge state, and cross-link enhanced emission effect for further understanding of complicated phenomena.

Controllable acidophilic dual-emission fluorescent carbonized polymer dots for selective imaging of bacteria.

Fluorescent materials can be powerful contrast agents in photoelectric devices and for bioimaging. As emerging fluorescent materials, carbonized polymer dots (CPDs) with high quantum yields (QYs), long-wavelength emission and multiple functions are highly desired. Despite great progress in the synthetic methods and QYs of CPDs, multiple emission of CPDs is challenging. Therefore, we developed CPDs with dual-emission fluorescence in terms of inherent blue and red emission. In addition, CPDs with sole blue emission (B-CPDs) and red emission (R-CPDs) were synthesized, respectively, by regulating the reaction conditions to control the quantitative structure and emission centers. The absolute QY of R-CPDs in water was 24.33%. These three types of CPDs with dual/sole emission could be used in optoelectronic and bioimaging applications. With different CPDs coated on a commercially available gallium nitride light-emitting diode chip as a color-conversion layer, LEDs with blue, yellow, and red emission were achieved. Benefiting from the different emission intensities and emission peaks of R/B-CPDs in different pH conditions, they were used (without further modification) to distinguish between Porphyromonas gingivalis, Streptococcus mutans, Escherichia coli and Staphylococcus aureus in dental plaque biofilms (the first time this has been demonstrated). These findings could enable a new development direction of CPDs based on the design of multi-emission centers.

A Rationally Designed Semiconducting Polymer Brush for NIR-II Imaging-Guided Light-Triggered Remote Control of CRISPR/Cas9 Genome Editing.

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has shown great potential in biomedical applications. Although physical approaches, viruses, and some nonviral vectors have been employed for CRISPR/Cas9 delivery and induce some promising genome-editing efficacy, precise genome editing remains challenging and has not been reported yet. Herein, second near-infrared window (NIR-II) imaging-guided NIR-light-triggered remote control of the CRISPR/Cas9 genome-editing strategy is reported based on a rationally designed semiconducting polymer brush (SPPF). SPPF can not only be a vector to deliver CRISPR/Cas9 cassettes but also controls the endolysosomal escape and payloads release through photothermal conversion under laser irradiation. Upon laser exposure, the nanocomplex of SPPF and CRISPR/Cas9 cassettes induces effective site-specific precise genome editing both in vitro and in vivo with minimal toxicity. Besides, NIR-II imaging based on SPPF can also be applied to monitor the in vivo distribution of the genome-editing system and guide laser irradiation in real time. Thus, this study offers a typical paradigm for NIR-II imaging-guided NIR-light-triggered remote control of the CRISPR/Cas9 system for precise genome editing. This strategy may open an avenue for CRISPR/Cas9 genome-editing-based precise gene therapy in the near future.

Fluorescent non-conjugated polymer dots for targeted cell imaging.

Through the chemical crosslinking of the sub-fluorophore, linear non-conjugated polymers can possess strong photoluminescence (PL), which is a very important fluorescence behavior and the non-conjugated polymer dots (PDs) are efficient bio-fluorophores for bio-based applications. Herein, the new type of non-conjugated polyethyleneimine (PEI) PDs was further modified by targeting molecules (folic acid) for a new generation of bio-fluorophores. The free folic acid can quench the PL of PDs by energy transfer, while the conjugated folic acid@PDs (FA@PDs) can still maintain their PL properties to a certain degree. The FA@PDs also possess lower toxicity compared with free PDs, which is possibly due to blocking of the amino groups. Moreover, we investigated the targeted bioimaging applications of the FA@PDs, which gave a very important direction for application of these types of materials.

The crosslink enhanced emission (CEE) in non-conjugated polymer dots: from the photoluminescence mechanism to the cellular uptake mechanism and internalization.

The crosslink enhanced emission (CEE) in a new type of non-conjugated polymer dots (PDs) is proved. The enhanced PL originates from the decreased vibration and rotation of amino-based chromophores. Furthermore, the cellular uptake mechanism and internalization of PDs were investigated in detail.

Elliptical polymer brush ring array mediated protein patterning and cell adhesion on patterned protein surfaces.

This paper presents a novel method to fabricate elliptical ring arrays of proteins. The protein arrays are prepared by covalently grafting proteins to the polymer brush ring arrays which are prepared by the techniques combining colloidal lithography dewetting and surface initiated atom-transfer radical polymerization (SI-ATRP). Through this method, the parameters of protein patterns, such as height, wall thickness, periods, and distances between two elliptical rings, can be finely regulated. In addition, the sample which contains the elliptical protein ring arrays can be prepared over a large area up to 1 cm(2), and the protein on the ring maintains its biological activity. The as-prepared ring and elliptical ring arrays (ERAs) of fibronectin can promote cell adhesion and may have an active effect on the formation of the actin cytoskeleton.

Biomimetic polyimide nanotube arrays with slippery or sticky superhydrophobicity.

In this paper, we report the fabrication of superhydrophobic polyimide (PI) nanotube arrays with different topographies, which possess slippery or "sticky" superhydrophobicity. The PI nanotube arrays were fabricated by the porous alumina membrane molding method. We regulated three kinds of solvent evaporation and drying processes, which controlled different congregated and noncongregated topographies of PI nanotube arrays. Large scale comb-like congregated topography possesses a small sliding angle (SA<5 degrees), small scale comb-like congregated topography possesses a medium sliding angle (SA is about 30 degrees), noncongregated topography possesses a large sliding angle (strong adhesive force to water droplet). Moreover, the as-prepared superhydrophobic PI nanotube arrays have remarkable resistivity to acid, weak base, high temperature (up to 350 degrees C) and various organic solvents. Our work provides a facile and promising strategy to fabricate superhydrophobic surfaces with controlled sliding angles by utilizing self-organization effect, and such high performance superhydrophobic PI nanotube arrays can be used as coating materials in various harsh conditions.