Near-infrared Biological Window Research Articles

Degradable bifunctional phototherapy composites based on upconversion nanoparticle-metal phenolic network for multimodal tumor therapy in the near-infrared biowindow

Phototherapy has garnered increasing attention as it allows for precise treatment of tumor sites with its accurate spatiotemporal control. In this study, we have successfully synthesized degradable bifunctional phototherapy agents (UCNPs@mSiO2@MPN-MC540/DOX) based on upconversion nanoparticle (UCNPs) and metal phenolic network (MPN), serving as a novel nanoplatform for multimodal tumor treatment in the near-infrared (NIR) biological window. To address the issue of low light penetration depth, the UCNPs we synthesized exhibited efficient light conversion ability under 808 nm laser irradiation to activate the photosensitizer Merocyanine 540 (MC540) for photodynamic therapy. Simultaneously, the 808 nm NIR light can also excite the MPN layer to achieve photothermal therapy for tumors. Additionally, the MPN layer possesses the capability of self-degradation under weakly acidic conditions. Within the tumor microenvironment, the MPN layer gradually degrades, facilitating the controlled release of the chemotherapy drug doxorubicin (DOX), thus achieving pH-responsive drug release and reducing the side effects of chemotherapy. This study provides an example of NIR-excited multimodal tumor treatment and pH-responsive drug release, offering a therapy model for precise tumor therapy.

Light Absorption Analysis and Optimization of Ag@TiO2 Core-Shell Nanospheroid and Nanorod.

For photothermal therapy of cancer, it is necessary to find Ag @TiO2 core-shell nanoparticles that can freely tune the resonance wavelength within the near-infrared biological window. In this paper, the finite element method and the size-dependent refractive index of metal nanoparticles were used to theoretically investigate the effects of the core material, core length, core aspect ratio, shell thickness, refractive index of the surrounding medium, and the particle orientation on the light absorption properties of Ag@TiO2 core-shell nanospheroid and nanorod. The calculations show that the position and intensity of the light absorption resonance peaks can be freely tuned within the first and second biological windows by changing the above-mentioned parameters. Two laser wavelengths commonly used in photothermal therapy, 808 nm (first biological window) and 1064 nm (second biological window), were selected to optimize the core length and aspect ratio of Ag@TiO2 core-shell nanospheroid and nanorod. It was found that the optimized Ag@TiO2 core-shell nanospheroid has a stronger light absorption capacity at the laser wavelengths of 808 nm and 1064 nm. The optimized Ag@TiO2 core-shell nanoparticles can be used as ideal therapeutic agents in photothermal therapy.

Benzobisthiadiazole-Based Small Molecular Near-Infrared-II Fluorophores: From Molecular Engineering to Nanophototheranostics.

Organic fluorescent molecules with emission in the second near-infrared (NIR-II) biological window have aroused increasing investigation in cancer phototheranostics. Among these studies, Benzobisthiadiazole (BBT), with high electron affinity, is widely utilized as the electron acceptor in constructing donor-acceptor-donor (D-A-D) structured fluorophores with intensive near-infrared (NIR) absorption and NIR-II fluorescence. Until now, numerous BBT-based NIR-II dyes have been employed in tumor phototheranostics due to their exceptional structure tunability, biocompatibility, and photophysical properties. This review systematically overviews the research progress of BBT-based small molecular NIR-II dyes and focuses on molecule design and bioapplications. First, the molecular engineering strategies to fine-tune the photophysical properties in constructing the high-performance BBT-based NIR-II fluorophores are discussed in detail. Then, their biological applications in optical imaging and phototherapy are highlighted. Finally, the current challenges and future prospects of BBT-based NIR-II fluorescent dyes are also summarized. This review is believed to significantly promote the further progress of BBT-derived NIR-II fluorophores for cancer phototheranostics.

(Invited) Manipulating Light Emission from Rare Earth Doped Nanoparticles for Applications in Theranostics

Luminescent nanomaterials that can be excited, as well as emit, in the near-infrared (NIR) have been investigated for use in a plethora of applications including nanomedicine, nanoelectronics, biosensing, bioimaging, photovoltaics, photocatalysis, etc. The use of NIR light for excitation mitigates some of the drawbacks associated with high-energy (UV or blue) excitation, for example, little to no background autofluorescence from the specimen under investigation as well as no incurred photodamage. Moreover, one of the biggest limitations is of course, that of penetration. As such, NIR light can penetrate tissues much better than high-energy light especially when these wavelengths lie within the three biological windows (BW-I: 700-950, BW-II: 1000-1350, BW-III: 1550-1870 nm) where tissues are optically transparent. At the forefront of NIR excited nanomaterials are rare earth doped nanoparticles, which due to their 4f electronic energy states can undergo conventional (Stokes) luminescence and emit in the three NIR biological windows. However, unlike other classes of nanoparticles, they can also undergo a multiphoton process (known as upconversion) where the NIR excitation light is converted to higher energies resulting in anti-Stokes luminescence spanning the UV-visible-NIR regions. Perhaps the biggest impact of such materials would be in the field of disease diagnostics and therapeutics, now commonly referred to as theranostics. Due to the versatility of their optical properties, it now becomes possible to generate high-energy light (UV or blue) in situ to trigger other light activated therapeutic modalities (i.e. drug release) while using the NIR emission for diagnostics (i.e. bioimaging, nanothermometry). Here, we present the synthesis of various NIR excited (and emitting) rare earth doped core/shell (and multishell) nanoparticles and demonstrate how their luminescence properties can be exploited for potential use in diverse biomedical applications.

Mn5+-doped BaAl2O4, Ba3Al2O6, and Ba7Al2O10 phosphors emitting in the second near-infrared biological window

In recent years, NIR-II-type fluorophores with emission wavelengths within the 1000–1700 nm range have garnered widespread attention in the field of bioimaging due to their high tissue penetration ability. Here, Mn-doped BaAl2O4, Ba3Al2O6, and Ba7Al2O10 with NIR-II-type luminescence were synthesized by solid-phase or liquid-phase methods. Confirmed by XPS and EDS analysis, Mn is found uniformly distributed in the structure in the valence state of + 5. The optimal doping concentration of Mn5+ in the three matrices was analyzed by PLE and PL spectroscopy. In addition, the samples exhibit a wide excitation range spanning from 600 to 900 nm, coupled with a narrow emission band peaking between 1150 and 1200 nm. As both the excitation and emission wavelengths have excellent penetration capabilities in biological tissues, the synthesized fluorescent phosphors in this study hold potential for meaningful applications in the realm of fluorescence imaging.

Enhancing in vitro photothermal therapy using plasmonic gold nanorod decorated multiwalled carbon nanotubes.

Photothermal therapy (PTT) is a promising approach for cancer treatment that selectively heats malignant cells while sparing healthy cells. Here, the light-to-heat conversion efficiency of multiwalled carbon nanotubes (MWCNTs) within the near-infrared biological transmission window is enhanced by decorating them with plasmonic gold nanorods (GNRs). The results reveal a significant photothermal enhancement of hybrid MWCNTs-GNRs compared to bare MWCNTs, displaying a 4.9 enhancement factor per unit mass. The enhanced plasmonic PTT properties of MWCNTs-GNRs are also investigated in vitro using PC3 prostate cancer cell lines, demonstrating a potent ablation efficiency. These findings advance innovative hybrid plasmonic nanostructures for clinical applications.

Gold Nanobipyramids for Near-Infrared Fluorescence-Enhanced Imaging and Treatment of Triple-Negative Breast Cancer.

There is an imminent need for novel strategies for the diagnosis and treatment of aggressive triple-negative breast cancer (TNBC). Cell-targeted multifunctional nanomaterials hold great potential, as they can combine precise early-stage diagnosis with local therapeutic delivery to specific cell types. In this study, we used mesoporous silica (MS)-coated gold nanobipyramids (MS-AuNBPs) for fluorescence imaging in the near-infrared (NIR) biological window, along with targeted TNBC treatment. Our MS-AuNBPs, acting partly as light amplification components, allow considerable metal-enhanced fluorescence for a NIR dye conjugated to their surfaces compared to the free dye. Fluorescence analysis confirms a significant increase in the dye's modified quantum yield, indicating that MS-AuNBPs can considerably increase the brightness of low-quantum-yield NIR dyes. Meanwhile, we tested the chemotherapeutic efficacy of MS-AuNBPs in TNBC following the loading of doxorubicin within the MS pores and functionalization to target folate receptor alpha (FRα)-positive cells. We show that functionalized particles target FRα-positive cells with significant specificity and have a higher potency than free doxorubicin. Finally, we demonstrate that FRα-targeted particles induce stronger antitumor effects and prolong overall survival compared to the clinically applied non-targeted nanotherapy, Doxil. Together with their excellent biocompatibility measured in vitro, this study shows that MS-AuNBPs are promising tools to detect and treat TNBCs.

Tunable Nanoparticles with Aggregation-Induced Emission Heater for Precise Synergistic Photothermal and Thermodynamic Oral Cancer Therapy of Patient-Derived Tumor Xenograft.

The fluorophores in the second near-infrared (NIR-II) biological window (1000 - 1700nm) show great application prospects in the fields of biology and optical communications. However, both excellent radiative transition and nonradiative transition cannot be achieved simultaneously for the majority of traditional fluorophores. Herein, tunable nanoparticles formulated with aggregation-induced emission (AIE) heater are developed rationally. The system can be implemented via the development of an ideal synergistic system that can not only produce photothermal from nonspecific triggers but also trigger carbon radical release. Once accumulating in tumors and subsequently being irradiated with 808nm laser, the nanoparticles (NMB@NPs) encapsulated with NMDPA-MT-BBTD (NMB) are splitted due to the photothermal effect of NMB, leading to the decomposition of azo bonds in the nanoparticle matrix to generate carbon radical. Accompanied by second near-infrared (NIR-II) window emission from the NMB, fluorescence image-guided thermodynamic therapy (TDT) and photothermal therapy (PTT) which significantly inhibited the growth of oral cancer and negligible systemic toxicity is achieved synergistically. Taken together, this AIE luminogens-based synergistic photothermal-thermodynamic strategy brings a new insight into the design of superior versatile fluorescent NPs for precise biomedical applications and holds great promise to enhance the therapeutic efficacy of cancer therapy.

Efficient Tumor Eradication at Ultralow Drug Concentration via Externally Controlled and Boosted Metallic Iron Magnetoplasmonic Nanocapsules.

With the aim to locally enhance the efficacy of cancer nanotherapies, here we present metal iron based magnetoplasmonic drug-loaded nanocapsules (MAPSULES), merging powerful external magnetic concentration in the tumor and efficient photothermal actuation to locally boost the drug therapeutic action at ultralow drug concentrations. The MAPSULES are composed of paclitaxel-loaded polylactic-co-glycolic acid (PLGA) nanoparticles partially coated by a nanodome shape iron/silica semishell. The iron semishell has been designed to present a ferromagnetic vortex for incorporating a large quantity of ferromagnetic material while maintaining high colloidal stability. The large iron semishell provides very strong magnetic manipulation via magnetophoretic forces, enabling over 10-fold higher trapping efficiency in microfluidic channels than typical superparamagnetic iron oxide nanoparticles. Moreover, the iron semishell exhibits highly damped plasmonic behavior, yielding intense broadband absorbance in the near-infrared biological windows and photothermal efficiency similar to the best plasmonic nanoheaters. The in vivo therapeutic assays in a mouse xenograft tumor model show a high amplification of the therapeutic effects by combining magnetic concentration and photothermal actuation in the tumor, leading to a complete eradication of the tumors at ultralow nanoparticle and drug concentration (equivalent to only 1 mg/kg PLGA nanoparticles containing 8 μg/kg of paclitaxel, i.e., 100-500-fold lower than the therapeutic window of the free and PLGA encapsulated drug and 13-3000-fold lower than current nanotherapies combining paclitaxel and light actuation). These results highlight the strength of this externally controlled and amplified therapeutic approach, which could be applied to locally boost a wide variety of drugs for different diseases.

Core−shell structured hollow copper sulfide@metal−organic framework for magnetic resonance imaging guided photothermal therapy in second near-infrared biological window

Multifunctional core-shell hybrids formed by integration of metal-organic framework (MOF) and functional materials have attracted extensive attention as promising theranostic nanoplatforms due to their combined novel properties and enhanced therapeutic efficacy. Recently, the second near-infrared (NIR-II, 1000–1700 nm) laser-induced photothermal therapy (PTT) as compared to the NIR-I(700–950 nm) laser-induced PTT has displayed improved therapeutic effects owing to its merits that include deeper tissue penetration and increased maximum permissible exposure. Herein, a novel core-shell hollow copper sulfide@metal−organic framework (HCuS@MIL-100) has been successfully fabricated by a layer-by-layer technique for the first time and their collective theranostic effects are investigated in vitro and in vivo. In this platform, the inner HCuS was applied as the NIR-II photothermal agent with excellent NIR-II absorption feature, leading to impressive photothermal effects under irradiation by 1064 nm light. With MIL-100 as the shell, HCuS@MIL-100 not only displayed optimal biocompatibility but also presented superior T2 magnetic resonance imaging (MRI) ability. In the current study multifunctional hollow core-shell HCuS@MIL-100 are fabricated for the MRI-guided PTT. This study also offers a facile and effective strategy for the development of novel theranostic platforms with high efficiency through the integration of MOFs and functional materials.

(Invited) Rare Earth Doped Nanoparticles

Luminescent nanomaterials that can be excited, as well as emit, in the near-infrared (NIR) have been investigated for use in a plethora of applications including nanomedicine, nanoelectronics, biosensing, bioimaging, photovoltaics, photocatalysis, etc. The use of NIR light for excitation mitigates some of the drawbacks associated with high-energy (UV or blue) excitation, for example, little to no background autofluorescence from the specimen under investigation as well as no incurred photodamage. Moreover, one of the biggest limitations is of course, that of penetration. As such, NIR light can penetrate tissues much better than high-energy light especially when these wavelengths lie within the three biological windows (BW-I: 700-950, BW-II: 1000-1350, BW-III: 1550-1870 nm) where tissues are optically transparent. At the forefront of NIR excited nanomaterials are rare earth doped nanoparticles, which due to their 4f electronic energy states can undergo conventional (Stokes) luminescence and emit in the three NIR biological windows. However, unlike other classes of nanoparticles, they can also undergo a multiphoton process (known as upconversion) where the NIR excitation light is converted to higher energies resulting in anti-Stokes luminescence spanning the UV-visible-NIR regions. Perhaps the biggest impact of such materials would be in the field of disease diagnostics and therapeutics, now commonly referred to as theranostics. Due to the versatility of their optical properties, it now becomes possible to generate high-energy light (UV or blue) in situ to trigger other light activated therapeutic modalities (i.e. drug release) while using the NIR emission for diagnostics (i.e. bioimaging, nanothermometry). Here, we present the synthesis of various NIR excited (and emitting) rare earth doped core/shell (and multishell) nanoparticles and demonstrate how their luminescence properties can be exploited for potential use in diverse biomedical applications.

Engineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapy

BackgroundAs an emerging therapeutic modality, chemodynamic therapy (CDT), converting hydrogen peroxide (H2O2) into highly toxic reactive oxygen species (ROS), has been developed for tumor-specific therapy. However, the deficiency of endogenous H2O2 and high concentration of glutathione (GSH) in the tumor microenvironment (TME) weaken the CDT-based tumor-therapeutic efficacy. Herein, a photothermal-enhanced tumor-specific cascade catalytic nanosystem has been constructed on the basis of glucose oxidase (GOD)-functionalized molybdenum (Mo)-based polyoxometalate (POM) nanoclusters, termed as GOD@POMs.MethodsGOD@POMs were synthesized by a facile one-pot procedure and covalently conjugation. Then, its structure was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). In addition, ultraviolet-visible-near-infrared (UV-vis-NIR) absorption spectrum and infrared thermal camera were applied to evaluate the catalytic and photothermal performance, respectively. Moreover, to confirm the therapeutic effects in vitro, cell counting kit-8 (CCK-8) assay, live/dead staining and ROS staining were performed. Furthermore, the biosafety of GOD@POMs was investigated via blood routine, blood biochemistry and hematoxylin and eosin (H&E) staining in Kunming mice. Besides, the C6 glioma tumor-bearing mice were constructed to evaluate its anti-tumor effects in vivo and its photoacoustic (PA) imaging capability. Notably, RNA sequencing, H&E, TdT-mediated dUTP nick end labeling (TUNEL) and Ki-67 staining were also conducted to disclose its underlying anti-tumor mechanism.ResultsIn this multifunctional nanosystem, GOD can effectively catalyze the oxidation of intratumoral glucose into gluconic acid and H2O2, achieving the cancer starvation therapy. Meanwhile, the generated gluconic acid decreases the pH in TME resulting in POM aggregation, which enables PA imaging-guided tumor-specific photothermal therapy (PTT), especially in the second near-infrared (NIR-II) biological window. Importantly, the Mo (VI) sites on POM can be reduced to Mo (V) active sites in accompany with GSH depletion, and then the post-produced Mo (V) transforms in situ overproduced H2O2 into singlet oxygen (1O2) via Russell mechanism, achieving self-enhanced CDT. Moreover, the PTT-triggered local tumor temperature elevation augments the synergistic nanocatalytic-therapeutic efficacy.ConclusionsConsequently, the integration of GOD-induced starvation therapy, H2O2 self-supply/GSH-depletion enhanced Mo-based CDT, and POM aggregation-mediated PTT endow the GOD@POMs with remarkable synergistic anticancer outcomes with neglectable adverse effects.

J-aggregates albumin-based NIR-II fluorescent dye nanoparticles for cancer phototheranostics.

Phototheranostics, relying on energy conversions of fluorophores upon excitation, integrating diagnostic fluorescence imaging and photo-driven therapy, represents a promising strategy for cancer precision medicine. Compared with the first near-infrared biological window (NIR-I), fluorophores imaged in the second window (NIR-II, 1000–1700 ​nm) exhibit a higher temporal and spatial resolution and tissue penetration depth. Polymethine cyanine-based dye IR1061 is a typical NIR-II small-molecule organic fluorophore, but its low water solubility and short circulation time limiting its biological applications. Therefore, human serum albumin (HSA) nanoparticles with great biocompatibility and biosafety were employed to fabricate hydrophobic IR1061, which exhibited red-shifted absorption band as typical for J-aggregates. Moreover, IR1061@HSA nanoparticles can be successfully used for NIR-II imaging to noninvasively visualize the tumor vascular networks, as well as real-time intraoperative image-guided tumor resection. Interestingly, benefiting from the high photothermal conversion efficiency brought by J-aggregates, IR1061@HSA nanoparticles were also explored for photothermal therapy (PTT) and cause efficient thermal ablation of tumors. Overall, IR1061@HSA, as a novel J-aggregates albumin-based NIR II dye nanoparticle with high biocompatibility, provides an integrated versatile platform for cancer phototheranostics with promising clinical translation prospects.

(Invited) Multi-Architectured Lanthanide Doped Nanoparticles for Theranostics

Light triggered theranostic (therapy and diagnostic) nanoplatforms have gained a considerable attention in recent years. In theranostics, light as an external trigger stands out due to its non-invasiveness, high local precision and temporal resolution. Many such nanoplatforms employ high-energy (visible or UV) light to initiate the individual therapeutic and diagnostic modalities. However, light at these wavelengths suffers from inherent drawbacks such as having little to no penetration in living tissue, inducing autofluorescence from inherent fluorophores or chromophores in tissues and causing photodamage. The use of near-infrared (NIR) light for excitation mitigates such drawbacks associated with high-energy excitation, for example, little to no background autofluorescence from the specimen under investigation as well as no incurred photodamage. Moreover, one of the biggest limitations is that of penetration and NIR light can penetrate tissues much better than high-energy light especially when these wavelengths lie within the three biological windows where tissues are optically transparent. At the forefront of NIR excited nanomaterials are lanthanide doped nanoparticles, which can undergo conventional (Stokes) luminescence and emit in the NIR biological windows. However, unlike other classes of nanoparticles, they can also undergo a multiphoton excitation process where the NIR excitation light is converted to higher energies resulting in anti-Stokes luminescence spanning the UV-visible-NIR regions (known as upconversion). Thus, it now becomes possible to generate upconverted high-energy light (UV or visible) in situ to trigger other light activated therapeutic modalities (i.e. drug release) while using the NIR emission for diagnostics (i.e. bioimaging, nanothermometry). Here, we demonstrate how the luminescence properties (upconversion and NIR) of various lanthanide doped core/shell (and multishell) nanoparticles can be exploited for potential use in theranostics.

Bimetallic oxide nanozyme-mediated depletion of glutathione to boost oxidative stress for combined nanocatalytic therapy

Although nanocatalytic therapy has become an emerging strategy for tumor treatment, the therapeutic effects of reactive oxygen species (ROS)-mediated treatment are still seriously limited by the inherent flaws of the enzymatic activities and the specific physicochemical properties of the tumor microenvironment (TME). Herein, we report an ultrasmall bimetallic oxide nanozyme (CuFe2O4@PEG, CFOs) for programmable multienzyme-like activities-primed combined therapy. Under the acidic condition, abundant highly toxic ROS can be generated through the peroxidase activity of CFOs with overexpressed hydrogen peroxide (H2O2) in the tumor. High metal ion utilization of bimetallic oxide nanozymes is related to the size effect and topological structure. Furthermore, glutathione peroxidase activity-initiated depletion of GSH disrupts the intracellular antioxidant defense system and further amplifies the oxidative stress in turn. Subsequently, oxygen generation originating from the catalase activity of CFOs relieves tumor hypoxia and achieves exceptional TME-customized therapeutic effects. Notably, the high photothermal effect (η = 41.12%) of CFOs in the second near-infrared biological windows leads to the combinational inhibition of tumor growth. In summary, this report provides a paradigm for the rational design of TME-responsive and ROS-mediated nanocatalytic treatment, which is promising for achieving superior therapeutic efficiency.

Fe3O4@Au@Cu2−xS Heterostructures Designed for Tri‐Modal Therapy: Photo‐ Magnetic Hyperthermia and 64Cu Radio‐Insertion

Here, the synthesis and proof of exploitation of three-material inorganic heterostructures made of iron oxide-gold-copper sulfide (Fe3 O4 @Au@Cu2- x S) are reported. Starting with Fe3 O4 -Au dumbbell heterostructure as seeds, a third Cu2- x S domain is selectively grown on the Au domain. The as-synthesized trimers are transferred to water by a two-step ligand exchange procedure exploiting thiol-polyethylene glycol to coordinate Au and Cu2- x S surfaces and polycatechol-polyethylene glycol to bind the Fe3 O4 surface. The saline stable trimers possess multi-functional properties: the Fe3 O4 domain, of appropriate size and crystallinity, guarantees optimal heating losses in magnetic hyperthermia (MHT) under magnetic field conditions of clinical use. These trimers have indeed record values of specific adsorption rate among the inorganic-heterostructures so far reported. The presence of Au and Cu2- x S domains ensures a large adsorption which falls in the first near-infrared (NIR) biological window and is here exploited, under laser excitation at 808nm, to produce photo-thermal heat alone or in combination with MHT obtained from the Fe3 O4 domain. Finally, an intercalation protocol with radioactive 64 Cu ions is developed on the Cu2- x S domain, reaching high radiochemical yield and specific activity making the Fe3 O4 @Au@Cu2- x S trimers suitable as carriers for 64 Cu in internal radiotherapy (iRT) and traceable by positron emission tomography (PET).

Geometric effects of plasmonic nanoscale heterostructures on infrared activity

Electron probes can resolve bright and dark optical modes at subwavelength scales to distinguish localized effects, e.g., those of composition and geometry, via energy loss measurements. In this work, electron energy loss spectra of a metal nanospheroid (NS) near a van der Waals material were simulated to show effects of NS shape and structure on plasmon and exciton energies. Hollowing or elongating the NS intensified and shifted its plasmon bright and dark mode energy losses. Simultaneous hollowing and elongation intensified and redshifted bifurcated bright modes more than adding effects of separate alterations, whereas the dark mode intensified additively and redshifted subadditively. Proximity to a transition metal dichalcogenide (TMD) nanodisk differentiated redshifting of bright modes (more) and dark (less) modes and fractured the modes across multiple spectral features. Some bright and dark mode energies were pinned at TMD exciton energies. Measured optical spectra exhibiting such effects corresponded to simulation. Only simultaneous hollowing and elongation above a TMD nanodisk redshifted primary components of each bright and dark mode entirely into the near-infrared (NIR) biological water window. Simulating energy electron loss spectra identifies nanoheterostructure geometry and composition that enhances bright- and dark-mode activity at biologically transparent NIR energies to potentiate bio/catalytic activity.

Boosting the Near-Infrared Emission of Ag2S Nanoparticles by a Controllable Surface Treatment for Bioimaging Applications.

Ag2S nanoparticles are the staple for high-resolution preclinical imaging and sensing owing to their photochemical stability, low toxicity, and photoluminescence (PL) in the second near-infrared biological window. Unfortunately, Ag2S nanoparticles exhibit a low PL efficiency attributed to their defective surface chemistry, which curbs their translation into the clinics. To address this shortcoming, we present a simple methodology that allows to improve the PL quantum yield from 2 to 10%, which is accompanied by a PL lifetime lengthening from 0.7 to 3.8 μs. Elemental mapping and X-ray photoelectron spectroscopy indicate that the PL enhancement is related to the partial removal of sulfur atoms from the nanoparticle’s surface, reducing surface traps responsible for nonradiative de-excitation processes. This interpretation is further backed by theoretical modeling. The acquired knowledge about the nanoparticles’ surface chemistry is used to optimize the procedure to transfer the nanoparticles into aqueous media, obtaining water-dispersible Ag2S nanoparticles that maintain excellent PL properties. Finally, we compare the performance of these nanoparticles with other near-infrared luminescent probes in a set of in vitro and in vivo experiments, which demonstrates not only their cytocompatibility but also their superb optical properties when they are used in vivo, affording higher resolution images.

An aza-BODIPY-based NIR-II luminogen enables efficient phototheranostics.

The fabrication of a high-performance second near-infrared (NIR-II) biological window fluorophore is in urgent need for precise diagnosis and treatment of cancer. Nevertheless, the construction of phototherapeutic agents in the NIR-II region with excellent imaging performance and minimal side effects remains a big challenge due to the limited availability of core fluorophore candidates. In this study, a new NIR-II fluorescent probe, CB1, which is an aza-BODIPY core conjugated with bulky donors, was designed and synthesized. CB1 was further encapsulated in DSPE-PEG2000 to impart water solubility, which shows brighter NIR-II fluorescence and higher photostability than the clinically used indocyanine green (ICG). CB1 nanoparticles show deep tissue penetration and high imaging contrast in vivo. In addition, molecular conformation enables CB1 nanoparticles to exhibit good photothermal properties. Both in vitro and in vivo assessments confirm that CB1 nanoparticles could be utilized as distinguished theranostic agents for NIR-II fluorescence imaging and tumor growth inhibition with negligible side effects. Collectively, this work provides a promising approach for constructing a new platform for cancer diagnosis and therapy.

Structure-Property-Function Relationships of Iron Oxide Multicore Nanoflowers in Magnetic Hyperthermia and Photothermia.

Magnetite and maghemite multicore nanoflowers (NFs) synthesized using the modified polyol-mediated routes are to date among the most effective nanoheaters in magnetic hyperthermia (MHT). Recently, magnetite NFs have also shown high photothermal (PT) performances in the most desired second near-infrared (NIR-II) biological window, making them attractive in the field of nanoparticle-activated thermal therapies. However, what makes magnetic NFs efficient heating agents in both modalities still remains an open question. In this work, we investigate the role of many parameters of the polyol synthesis on the final NFs' size, shape, chemical composition, number of cores, and crystallinity. These nanofeatures are later correlated to the magnetic, optical, and electronic properties of the NFs as well as their collective macroscopic thermal properties in MHT and PT to find relationships between their structure, properties, and function. We evidence the critical role of iron(III) and heating ramps on the elaboration of well-defined NFs with a high number of multicores. While MHT efficiency is found to be proportional to the average number of magnetic cores within the assemblies, the optical responses of the NFs and their collective photothermal properties depend directly on the mean volume of the NFs (as supported by optical cross sections numerical simulations) and strongly on the structural disorder in the NFs, rather than the stoichiometry. The concentration of defects in the nanostructures, evaluated by photoluminescence and Urbach energy (EU), evidence a switch in the optical behavior for a limit value of EU = 0.4 eV where a discontinuous transition from high to poor PT efficiency is also observed.