Exploring the effect of photobiomodulation and gamma visual stimulation induced by 808 nm and visible LED in Alzheimer's disease mouse model.

Although photobiomodulation (PBM) and gamma visual stimulatqion (GVS) have been overwhelmingly explored in the recent time as a possible light stimulation (LS) means of Alzheimer's disease (AD) therapy, their effects have not been assessed at once. In our research, the AD mouse model was stimulated using light with various parameters [continuous wave (PBM) or 40 Hz pulsed visible LED (GVS) or 40 Hz pulsed 808 nm LED (PBM and GVS treatment)]]. The brain slices collected from the LS treated AD model mice were evaluated using (i) fluorescence microscopy to image thioflavine-S labeled amy-loid-ß (Aß) plaques (the main hallmark of AD), or (ii) two-photon excited fluorescence (TPEF) imaging of unlabeled Aß plaques, showing that the amount of Aß plaques was reduced after LS treatment. The imaging results correlated well with the results of Morris water maze (MWM) test, which demonstrated that the spatial learning and memory abilities of LS treated mice were noticeably higher than those of untreated mice. The LS effect was also assessed by in vivo nonlinear optical imaging, revealing that the cerebral amyloid angiopathy decreased spe-cifically as a result of 40 Hz pulsed 808 nm irradiation, on the contrary, the angiopathy reversed after visible 40 Hz pulsed light treatment. The obtained results provide useful reference for further optimization of the LS (PBM or GVS) parameters to achieve efficient phototherapy of AD.

The Mechanisms and Efficacy of Photobiomodulation Therapy for Arthritis: A Comprehensive Review.

Rheumatoid arthritis (RA) and osteoarthritis (OA) have a significant impact on the quality of life of patients around the world, causing significant pain and disability. Furthermore, the drugs used to treat these conditions frequently have side effects that add to the patient's burden. Photobiomodulation (PBM) has emerged as a promising treatment approach in recent years. PBM effectively reduces inflammation by utilizing near-infrared light emitted by lasers or LEDs. In contrast to photothermal effects, PBM causes a photobiological response in cells, which regulates their functional response to light and reduces inflammation. PBM's anti-inflammatory properties and beneficial effects in arthritis treatment have been reported in numerous studies, including animal experiments and clinical trials. PBM's effectiveness in arthritis treatment has been extensively researched in arthritis-specific cells. Despite the positive results of PBM treatment, questions about specific parameters such as wavelength, dose, power density, irradiation time, and treatment site remain. The goal of this comprehensive review is to systematically summarize the mechanisms of PBM in arthritis treatment, the development of animal arthritis models, and the anti-inflammatory and joint function recovery effects seen in these models. The review also goes over the evaluation methods used in clinical trials. Overall, this review provides valuable insights for researchers investigating PBM treatment for arthritis, providing important references for parameters, model techniques, and evaluation methods in future studies.

Pr3+ doped NaYF4 and LiYF4 nanocrystals combining visible-to-UVC upconversion and NIR-to-NIR-II downconversion luminescence emissions for biomedical applications.

Lanthanide-doped fluoride nanocrystals (NCs) are known to exhibit unique optical properties, such as upconversion and downconversion luminescence (UCL and DCL), which can be employed for various applications. In this work, we demonstrate that by doping praseodymium(III) and ytterbium(III) ions (Pr3+ and Yb3+) into a nanosized fluoride matrix (i.e. NaYF4 and LiYF4), it is possible to combine their UCL and DCL properties that can be concurrently used for biomedical applications. In particular, the emissive modes combined in a single nanoparticle co-doped with Pr3+ and Yb3+ include DCL emission (excited at 980 nm and peaked at 1320 nm), which can be used for near infrared (NIR) DCL bioimaging in the NIR-II window of biological tissue transparency (∼1000-1350 nm) and UCL emission (excited at 447 nm and peaked at 275 nm) that can be employed for germicide action (via irradiation by light in the UVC range). A possibility of the latter was demonstrated by the denaturation of double-stranded DNA (dsDNA) into single-stranded ones that was caused by the UVC UCL emission from the NCs under 447 nm irradiation; it was evidenced by the hyperchromicity observed in the irradiated dsDNA solution and also by a fluorometric analysis of DNA unwinding (FADU) assay. Concurrently, the possibility of NIR-II luminescence bioimaging through biological tissues (bovine tooth and chicken flesh) was demonstrated. The proposed concept paves a way for NIR-II imaging guided antimicrobial phototherapy using lanthanide-doped fluoride nanocrystals.

Near-infrared light reduces ß-amyloid-stimulated microglial toxicity and enhances survival of neurons: mechanisms of light therapy for Alzheimer's disease.

BACKGROUND: Low-intensity light can decelerate neurodegenerative disease progression and reduce amyloid ß (Aß) levels in the cortex, though the cellular and molecular mechanisms by which photobiomodulation (PBM) protects against neurodegeneration are still in the early stages. Microglia cells play a key role in the pathology of Alzheimer's disease by causing chronic inflammation. We present new results concerning the PBM of both oxidative stress and microglia metabolism associated with the activation of metabolic processes by 808 nm near-infrared light. METHODS: The studies were carried out using healthy male mice to obtain the microglial cell suspension from the hippocampus. Oligomeric ß-amyloid (1-42) was prepared and used to treat microglia cells. Light irradiation of cells was performed using diode lasers emitting at 808 nm (30 mW/cm2 for 5 min, resulting in a dose of 10 J/cm2). Mitochondrial membrane potential, ROS level studies, cell viability, apoptosis, and necrosis assays were performed using epifluorescence microscopy. Phagocytosis, nitric oxide and H2O2 production, arginase, and glucose 6-phosphate dehydrogenase activities were measured using standard assays. Cytokines, glucose, lactate, and ATP were measurements with ELISA. As our data were normally distributed, two-way ANOVA test was used. RESULTS: The light induces a metabolic shift from glycolysis to mitochondrial activity in pro-inflammatory microglia affected by oligomeric Aß. Thereby, the level of anti-inflammatory microglia increases. This process is accompanied by a decrease in pro-inflammatory cytokines and an activation of phagocytosis. Light exposure decreases the Aß-induced activity of glucose-6-phosphate dehydrogenase, an enzyme that regulates the rate of the pentose phosphate pathway, which activates nicotinamide adenine dinucleotide phosphate oxidases to further produce ROS. During co-cultivation of neurons with microglia, light prevents the death of neurons, which is caused by ROS produced by Aß-altered microglia. CONCLUSIONS: These original data clarify reasons for how PBM protects against neurodegeneration and support the use of light for therapeutic research in the treatment of Alzheimer's disease.

Metallo-Dye-Based Supramolecular Nanoassembly for NIR-II Cancer Theranostics.

Retaining intrinsic photophysical performance and efficient therapeutic efficacy of cyanine dyes in the second near-infrared (NIR-II) biowindow are challenges in the biomedical field. Herein, we develop a metal ion-assisted NIR-II fluorophore assembly strategy to modulate molecular arrangement behavior, thus overcoming the drawbacks and retaining the photophysical performance of cyanine dyes in aqueous media for cancer phototheranostics. By screening a series of metal ion-assisted fluorophore assemblies, we remarkably found gadolinium-based metallo-dye-supramolecular nanoassembly (denoted as Gd@IR1064) with the intrinsic optical properties of NIR-II cyanine dye (IR1064). Most intriguingly, the as-prepared Gd@IR1064 not only exhibits deep-tissue-penetrating NIR-II photoacoustic, fluorescence, and magnetic resonance imaging ability but also possesses enhanced photothermal conversion performance-induced hyperthermia, achieving a significant tumor elimination effect. Our study provides a promising guide for modulating dye arrangement with unique photophysical performance for biomedical applications.

Red and near infrared light-stimulated angiogenesis mediated via Ca2+ influx, VEGF production and NO synthesis in endothelial cells in macrophage or malignant environments.

Irradiation with red or near-infrared (NIR) light in low level light therapy (LLLT) is found to stimulate cellular processes and bioenergetics, resulting in enhanced wound healing, pain control, neurodegenerative diseases treatment, etc. During light irradiation of tissues and organs, different cells are affected, though the connection between photostimulation of cells and their environmental conditions remains poorly understood. In this report, red/NIR light-stimulated angiogenesis is investigated using endothelial cells in vitro, with a focus on the capillary-like structure (CLS) formation and the respective biochemical processes in cells under conditions proximate to a healthy or malignant environment, which strongly defines angiogenesis. To model environmental conditions for endotheliocytes in vitro, the cell culture environment was supplemented by an augmented conditioned medium from macrophages or cancer cells. The biochemical processes in endothelial cell cultures were investigated with and without irradiation by red (650 nm) and near-infrared (808 nm) laser diodes and under normoxia or hypoxia conditions. A light-stimulated angiogenesis has been found, with a more efficient stimulation by 650 nm light compared to 808 nm light. It was shown that the irradiation with light promoted extracellular Ca2+ influx, fostered cell cycle progression, proliferation and NO generation in endothelial cells, and caused an increase in vascular endothelial growth factor (VEGF) production by endothelial cells and M2 macrophages under hypoxia conditions. The activation of VEGF production by macrophages was found to be associated with an increase in the number of M2 macrophages after light irradiation under hypoxia conditions. Thus, a new pathway of an activation of the endothelial cell metabolism, which is related with the extracellular Ca2+ influx after light irradiation, has been revealed. STATEMENT OF SIGNIFICANCE: Red/NIR light-stimulated angiogenesis has been studied using endothelial cells in vitro, with focus on CLS formation and the respective biochemical processes in cell models proximate to a healthy or malignant environment. A light-stimulated angiogenesis has been found, stimulated via extracellular Ca2+ influx, cell cycle progression, proliferation and NO generation, VEGF production increase by endothelial cells under hypoxia conditions.

Degradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics.

Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous structures cannot be obtained by the traditional template-mediated strategies due to the inevitable hydrolytic reaction of semimetal compounds. Therefore, it is yet challenging to fabricate mesoporous semimetal nanostructures, not even mention controlling their pore sizes. Here we develop a facile and robust selective etching route to synthesize monodispersed mesoporous antimony nanospheres (MSbNSs). The pore sizes of MSbNSs are tunable by carefully controlling the partial oxidation of Sb nuclei and the selective etching of the as-formed Sb2O3. MSbNSs show a wide absorption from visible to second near-infrared (NIR-II) region. Moreover, PEGylated MSbNSs are degradable and the degradation mechanism is further explained. The NIR-II photothermal performance of MSbNSs is promising with a high photothermal conversion efficiency of ~44% and intensive NIR-II photoacoustic signal. MSbNSs show potential as multifunctional nanomedicines for NIR-II photoacoustic imaging guided synergistic photothermal/chemo therapy in vivo. Our selective etching process would contribute to the development of various semimetallic mesoporous structures and efficient multimodal nanoplatforms for theranostics.

Macrophages Modulated by Red/NIR Light: Phagocytosis, Cytokines, Mitochondrial Activity, Ca2+ Influx, Membrane Depolarization and Viability.

Low-level light therapy (LLLT) is emerging as a promising therapeutic approach to modulate the biochemical and molecular processes within living cells. LLLT is known to produce local and systemic effects; therefore, immune cells in local tissues or in the circulation are affected by light. However, this specific effect remains weakly explored. In this study, the effect of red (650 nm) and NIR (808 nm) light on phagocytosis (respiratory burst), cytokine expression, mitochondrial activity, ROS generation, Ca2+ influx and membrane depolarization in macrophages in vitro is investigated. Both the phagocytic capacity and adhesion of macrophages strongly (~2.5 times) increased in the first hours after exposure to light in a dose-dependent manner. The light-evoked upregulation of phagocytosis is found to be less efficient than the maximal pharmacologically induced enhancement of ~3.2 times. Also, red/NIR light reduces the production of pro-inflammatory cytokines and activates the secretion of anti-inflammatory cytokines by several times in activated macrophages. At the same time, the viability shows a biphasic dose response: it increases after irradiation with lower doses (0.3-1 J cm-2 ) and decreases after treatment with higher doses (18-30 J cm-2 ), which is apparently associated with the upregulation of ROS generation, followed by an increase in the mitochondrial activity.

Synergistic interventional photothermal therapy and immunotherapy using an iron oxide nanoplatform for the treatment of pancreatic cancer.

Pancreatic cancer (PC) is the most lethal malignancy due to its high metastatic ability and poor drug permeability. Here, a synergized interventional photothermal-immunotherapy strategy was developed with imaging guidance and temperature monitoring by magnetic resonance imaging (MRI) technique, for the local treatment of metastatic PC. A tumor microenvironment (TME)-responsive nanoplatform was fabricated via coating of DSPE-PEG and indocyanine green (ICG) onto imiquimod (IMQ) loaded amorphous iron oxide nanoparticles (IONs). This unique nanoplatform, IMQ@IONs/ICG, served as a contrast agent for MRI, a drug delivery vehicle for IMQ and ICG, and a catalyst for TME modulation. The biodegradable IMQ@IONs/ICG was also non-toxic, and improved the penetration of the loaded drugs in PC to maximize thermal ablation of the tumor and minimize damage to the surrounding healthy tissue. For the treatment of aggressive, metastatic Panc02-H7 pancreatic tumors in mice, ION-assisted MRI was employed to guide the administration of interventional photothermal therapy (IPTT) and monitor the temperature distribution in target tumor and surrounding tissue during treatment. The local IPTT treatment induced in situ immunogenic cell death (ICD), and, in combination with released IMQ, triggered a strong antitumor immunity, leading to decreased metastases and increased CD8+ in spleen and tumors. With precise local treatment and monitoring, treated primary tumors were completely eradicated, mesentery metastases were dramatically reduced, and the survival time was significantly prolonged, without damage to normal tissue and systemic autoimmunity. Overall, this synergistic strategy represents a promising approach to treat PC with significant potential for clinical applications. STATEMENT OF SIGNIFICANCE: Pancreatic cancer (PC) is one of the most lethal malignancies because it is non-permeable to drugs and highly metastatic. In this study, we designed a tumor microenvironment-responsive amorphous iron oxide nanoplatform (ION) to co-deliver photothermal agent (ICG) and toll-like-receptor-7 agonist (IMQ). This biodegradable nanoplatform IMQ@IONs/ICG improved the penetration of the loaded drugs in pancreatic tumor. With MR imaging guidance and temperature monitoring, the precise interventional photothermal therapy on mouse Panc02-H7 orthotopic tumors releases tumor antigens to initiate tumor-special immune responses, amplified by the released IMQ. Our results demonstrate that IMQ@IONs/ICG overcomes the obstacle of drug delivery to pancreatic tumors, and when combined with photothermal therapy, induces a systemic antitumor immunity to control metastatic tumors.

Clinically translatable gold nanozymes with broad spectrum antioxidant and anti-inflammatory activity for alleviating acute kidney injury.

Rationale: Acute kidney injury (AKI) is associated with aberrant generation of oxidative species and inflammation, leading to high mortality of in-hospitalized patients. Although N-acetylcysteine (NAC) showed positive effects in alleviating contrast-induced AKI, the clinical applications are strongly restrained due to the low bioavailability, low renal accumulation, short renal retention time, and high dosage-induced toxicity. Methods: We addressed the clinical dilemma of NAC by developing ultrasmall gold nanoclusters (1-2 nm) capped with NAC (denoted as Au NCs-NAC) as a nanozyme-based antioxidant defense system for AKI alleviation. Rhabdomyolysis-induced AKI mice model was developed, and the same dose of free NAC (as a control) and NAC onto Au NCs (Au NCs-NAC) was used for in vivo investigation of AKI restoration. Results: The as-developed gold nanozyme exhibited high bioavailability and good physicochemical stability as compared to NAC. Meanwhile, Au NCs-NAC showed broad-spectrum antioxidant activity of Au NCs-NAC, offering in vitro renoprotective effects, as well as macrophages by relieving inflammation under hydrogen peroxide or lipopolysaccharide stimulation. Notably, owing to the smaller size than kidney threshold (5.5 nm), Au NCs-NAC displayed preferential renal enrichment (< 2 h) and longer retention (> 24 h) in AKI mice as revealed by fluorescence imaging, thereby largely enhancing the restoration of renal function in AKI mice than free NAC by protecting the kidneys from oxidative injury and inflammation without systemic toxicity, as demonstrated by tissues staining, inflammatory cytokines and biomarkers detection, and mice survival rate. Conclusion: Owing to the synergistic anti-inflammatory/antioxidative effects, and enhanced bioavailability and renal accumulation/retention, Au NCs-NAC displayed far superior therapeutic performance than NAC alone. This work will facilitate the development of high-performance antioxidative nanoplatforms, as well as overcome the clinical limitations of small molecular drugs for AKI treatment and other inflammatory diseases.

Catalase Nanocrystals Loaded with Methylene Blue as Oxygen Self-Supplied, Imaging-Guided Platform for Photodynamic Therapy of Hypoxic Tumors.

Photodynamic therapy (PDT) is a well-known method for cancer therapy in the clinic. However, the inherent hypoxia microenvironment of solid tumors enormously restricts the PDT efficiency. Herein, catalase nanocrystals (CatCry) are introduced as in situ oxygen (O2 )-generating system to relieve tumor hypoxia and enhance PDT efficiency for solid tumors. After loading with photosensitizer methylene blue (MB), a PDT drug platform (CatCry-MB) emerges, allowing for significant increasing PDT efficiency instigated by three factors. First, the high stability and recyclable catalytic activity of CatCry enable a long-term endogenous H2 O2 decomposition for continuous O2 supply for sustained relief of tumor hypoxia. Second, both the produced O2 and loaded MB are confined within CatCry nanoporous structure, shortening the diffusion distance between O2 and MB to maximize the production of singlet oxygen (1 O2 ). Third, the MB molecules are uniformly dispersed within CatCry lattice, avoiding MB aggregation and causing more MB molecules be activated to produce more 1 O2 . With the three complementary mechanisms, tumor hypoxia is eradicated and the resulted enhancement in PDT efficiency is demonstrated in vitro and in vivo. The proposed approach opens up a new venue for the development of other O2 -dependent tumor treatments, such as chemotherapy, radiotherapy, and immunotherapy.

Nitric oxide release activated near-Infrared photothermal agent for synergistic tumor treatment.

Activatable phototherapeutic agents (PTA) in one system with synergistic gas therapy (GT) and photothermal therapy (PTT) hold great promise for highly efficient tumor treatments. In this study, an activatable multifunctional platform with photothermal conversion "turn on" features via nitric oxide (NO) release for synergistic GT and PTT was rationally designed using an aryl N-nitrosamine (NO-donating unit) functionalized aza-BODIPY framework (S-NO). As expected, after NO release from S-NO, the product (Red-S) showed obviously enhanced heat production performance under a longer excited wavelength via improved near-infrared light absorption and decreased fluorescence emission. Furthermore, water-soluble and biocompatible S-NO nanoparticles (S-NO NPs) with negligible dark cytotoxicity successfully suppressed tumor growth and enhanced the survival rate of mice via synergistic GT and PTT under the guidance of multimode imaging. The study offered rational guidance to design better platforms for synergistic tumor treatments and validated that S-NO NPs can act as potential PTAs in biological applications.

MXene and black phosphorus based 2D nanomaterials in bioimaging and biosensing: progress and perspectives.

Bioimaging and biosensing have garnered interest in early cancer diagnosis due to the ability of gaining in-depth insights into cellular functions and providing a wide range of diagnostic parameters. Emerging 2D materials of multielement MXenes and monoelement black phosphorous nanosheets (BPNSs) with unique intrinsic physicochemical properties such as a tunable bandgap and layer-dependent fluorescence, high carrier mobility and transport anisotropy, efficient fluorescence quenching capability, desirable light absorption and thermoelastic properties, and excellent biocompatibility and biosafety properties provide promising nano-platforms for bioimaging and biosensing applications. In view of the growing attention on the rising stars of the post-graphene age in the progress of bioimaging and biosensing, and their common feature characteristics as well as complementarity for constructing complexes, the main objective of this review is to reveal the recent advances in the design of MXene or BPNS based nanoplatforms in the field of bioimaging and biosensing. The preparation and surface functionalization methods, biosafety, and other important aspects of bioimaging and biosensing applications of MXenes and BPNSs have been assessed systematically, along with highlighting the main challenges in further biomedical application. The review not only focuses on the advancements in 2D materials for use in bioimaging and biosensing but also assesses the possibility of their future potential in bioapplications.

Antimony Nanopolyhedrons with Tunable Localized Surface Plasmon Resonances for Highly Effective Photoacoustic-Imaging-Guided Synergistic Photothermal/Immunotherapy.

Antimony (Sb), a typical group VA semimetal, has rarely been studied both experimentally and theoretically in plasmonic photothermal therapy, possibly due to the lack of effective morphology-controllable methods for the preparation of high-quality Sb nanocrystals. In this study, an effective ligand-guided growth strategy to controllably synthesize Sb nanopolyhedrons (Sb NPHs) with ultrahigh photothermal conversion efficiency (PTCE), good photothermal stability, as well as biocompatibility is presented. Furthermore, the modulation effect of different morphologies on localized surface plasmon resonance (LSPR) of Sb NPHs in experimentation is successfully observed. When the resonance frequency of the Sb NPHs is matched well with the excitation wavelength (808 nm), the PTCE of the Sb NPHs is as high as 62.1%, which is noticeably higher compared to most of the reported photothermal agents. The Sb NPHs also exhibit good photothermal stability. In addition, Sb-NPHs-based multifunctional nanomedicines are further constructed via loading 1-methyl-d-tryptophan on PEGylated Sb NPHs for a highly efficient photoacoustic-imaging-guided synergistic photothermal/immune-therapy of tumors in vivo. This work can stimulate further theoretical and experimental investigations of Sb NPHs and other semimetal nanomaterials regarding their LSPR properties and inspire various potential applications of semimetals in biomedicine and sensors.

Photo-activated chemo-immunotherapy for metastatic cancer using a synergistic graphene nanosystem.

We developed a novel treatment strategy for metastatic cancer by synergizing photothermal therapy (PTT), chemotherapy, and immunotherapy through a nanosystem to trigger host antitumor immunity. The nanosystem was constructed by loading mitoxantrone (MTX), a chemotherapeutic agent, and SB-431542 (SB), a transforming growth factor beta (TGF-ß) inhibitor, onto reduced graphene oxide (rGO). Intratumoral administration of rGO/MTX/SB, followed by non-invasive irradiation of a near-infrared laser, destroyed local primary tumors and inhibited distant metastases in 4T1 mouse mammary tumor model, which is poorly immunogenic and highly metastatic. After treatment, 70% of the tumor-bearing mice became long-term survivors and developed a tumor type-specific immunity to resist rechallenged tumor cells. We found that rGO-based PTT provided an immunogenic antigen source, forming in situ vaccination with rGO as an immune-adjuvant. The use of SB changed the tumor microenvironment and improved the therapeutic effect of MTX-generated chemotherapy and rGO-based PTT. The immunological functions of MTX, SB, and rGO acted synergistically to induce an effective tumor vaccination, as evidenced by the increased infiltration of tumor-specific cytotoxic CD8+ T lymphocytes and decreased infiltration of regulatory T cells (Tregs) in distal tumors. Collectively, we demonstrated that rGO/MTX/SB combined with laser irradiation provided a synergistic chemo-immuno-photothermal effect against tumors by in situ vaccination and inhibition of immunosuppressive microenvironment. This unique combination embodies a promising approach to treat metastatic cancers by inducing a systemic antitumor response through a local intervention.

Red and near-infrared light evokes Ca2+ influx, endoplasmic reticulum release and membrane depolarization in neurons and cancer cells.

Low level light therapy uses light of specific wavelengths in red and near-infrared spectral range to treat various pathological conditions. This light is able to modulate biochemical cascade reactions in cells that can have important health implications. In this study, the effect of low intensity light at 650, 808 and 1064 nm on neurons and two types of cancer cells (neuroblastoma and HeLa) is reported, with focus on the photoinduced change of intracellular level of Ca2+ ions and corresponding signaling pathways. The obtained results show that 650 and 808 nm light promotes intracellular Ca2+ elevation regardless of cell type, but with different dynamics due to the specificities of Ca2+ regulation in neurons and cancer cells. Two origins responsible for Ca2+ elevation are determined to be: influx of exogenous Ca2+ ions into cells and Ca2+ release from endoplasmic reticulum. Our investigation of the related cellular processes shows that light-induced membrane depolarization is distinctly involved in the mechanism of Ca2+ influx. Ca2+ release from endoplasmic reticulum activated by reactive oxygen species generation is considered as a possible light-dependent signaling pathway. In contrast to the irradiation with 650 and 808 nm light, no effects are observed under 1064 nm irradiation. We believe that the obtained insights are of high significance and can be useful for the development of drug-free phototherapy.

Biodegradable pH-responsive amorphous calcium carbonate nanoparticles as immunoadjuvants for multimodal imaging and enhanced photoimmunotherapy.

Development of bioresponsive theranostic nanoparticles to enhance cancer diagnostics and control cancer metastasis is highly desirable. In this study, we developed such a bioresponsive theranostic nanoparticle for synergistic photoimmunotherapy. In particular, these nanoparticles were constructed by embedding indocyanine green (ICG) into Mn2+-doped amorphous calcium carbonate (ACC(Mn)) nanoparticles, followed by loading of the Toll-like-receptor-7 agonist imiquimod (IMQ). The IMQ@ACC(Mn)-ICG/PEG nanoparticles respond to the acidic pH of the tumor microenvironment (TME) and co-deliver ICG and IMQ into the tumor. Selective phototherapy was achieved upon activation using a near-infrared laser. In the presence of IMQ and arising from phototherapeutically treated tumor cells, tumor-associated antigens give rise to a strong antitumor immune response. Reversal of the immunosuppressive TME via H+ scavenging of the tumor through ACC nanoparticles effectively inhibits tumor metastases. Moreover, the combination of ICG and Mn2+ also serves as an advanced contrast agent for cancer multimode imaging. Overall, these bioresponsive nanoparticles provide a promising approach for cancer theranostics with promising potential for future clinical translation.

Co-encapsulating indocyanine green and CT contrast agent within nanoliposomes for trimodal imaging and near infrared phototherapy of cancer.

X-ray CT imaging can be complementary to fluorescence and photoacoustic imaging (FLI and PAI), allowing for high spatial resolution and high-sensitivity multimodal imaging for imaging guided treatment. In this study, the CT contrast agent iohexol was co-encapsulated with indocyanine green (ICG) within nanoliposomes (NLs) to explore their interaction and possible application of this liposomal formulation (LGI) in cancer theranostics. The photophysical properties of LGI were studied to assess the effect of iohexol on ICG that can enhance the efficiency of ICG-based near infrared photodynamic therapy (PDT). The CT, FLI and PA imaging abilities of LGI were also investigated. Furthermore, the near infrared phototherapy of cancer cells in vitro was performed, exhibiting higher phototherapy efficacy of LGI in comparison with other ICG formulations. We conclude that LGI can serve as a highly efficient theranostic nanoplatform for multimodal (fluorescence, CT and PA) imaging and near infrared phototherapy.

Ultrasensitive Surface Plasmon Resonance Biosensor Using Blue Phosphorus-Graphene Architecture.

This study theoretically proposed a novel surface plasmon resonance biosensor by incorporating emerging two dimensional material blue phosphorus and graphene layers with plasmonic gold film. The excellent performances employed for biosensing can be realized by accurately tuning the thickness of gold film and the number of blue phosphorus interlayer. Our proposed plasmonic biosensor architecture designed by phase modulation is much superior to angular modulation, providing 4 orders of magnitude sensitivity enhancement. In addition, the optimized stacked configuration is 42 nm Au film/2-layer blue phosphorus /4-layer graphene, which can produce the sharpest differential phase of 176.7661 degrees and darkest minimum reflectivity as low as 5.3787 × 10-6. For a tiny variation in local refractive index of 0.0012 RIU (RIU, refractive index unit) due to the binding interactions of aromatic biomolecules, our proposed biosensor can provide an ultrahigh detection sensitivity up to 1.4731 × 105 °/RIU, highly promising for performing ultrasensitive biosensing application.

Programming cell pyroptosis with biomimetic nanoparticles for solid tumor immunotherapy.

Immunotherapy shows remarkable efficacy in treating several types of cancer such as melanoma, leukemia, and lung carcinoma, but its therapeutic effect for most solid tumors is still limited. Various cancer therapies, such as chemotherapy, radiotherapy and phototherapy, kill solid tumors through non-inflammatory apoptosis or ablation, rather than making solid tumors immunogenic. As a highly-inflammatory programmed cell death (PCD), pyroptosis provides a great opportunity to alleviate immunosuppression and promote a systemic immune response in treating solid tumors. Herein, by fusing breast cancer membrane onto the poly(lactic-co-glycolic acid) polymeric core, we design a biomimetic nanoparticle (BNP) loaded with indocyanine green (ICG) and decitabine (DCT) for photo-activated cancer cell pyroptosis and solid tumor immunotherapy. The tumor-homing BNP effectively accumulate in tumor with low immunogenicity. ICG in BNP puncture cancer cell membranes induces a sharp cytoplasm Ca2+ concentration increase by low-dose NIR photo-activation, which promotes cytochrome c release followed by caspase-3 activation. DCT up-regulates GSDME expression synergistically via inhibiting DNA methylation, which enhances caspase-3 cleavage to GSDME and causes cancer cell pyroptosis. Finally, photo-activated pyroptosis mediated by BNP induces an impressive systemic antitumor immunity for inhibition of both primary tumor and distant tumors. Overall, pyroptosis-associated BNP shows a novel strategy for solid tumor immunotherapy with high compatibility and wide clinical applicability.