Advancing insights into in vivo meningeal lymphatic vessels with stereoscopic wide-field photoacoustic microscopy.

Meningeal lymphatic vessels (mLVs) play a pivotal role in regulating metabolic waste from cerebrospinal fluid (CSF). However, the current limitations in field of view and resolution of existing imaging techniques impede understanding the stereoscopic morphology and dynamic behavior of mLVs in vivo. Here, we utilized dual-contrast functional photoacoustic microscopy to achieve wide-field intravital imaging of the lymphatic system, including mLVs and glymphatic pathways. The stereoscopic photoacoustic microscopy based on opto-acoustic confocal features has a depth imaging capability of 3.75 mm, facilitating differentiation between mLVs on the meninges and glymphatic pathways within the brain parenchyma. Subsequently, using this imaging technique, we were able to visualize the dynamic drainage of mLVs and identify a peak drainage period occurring around 20-40 min after injection, along with determining the flow direction from CSF to lymph nodes. Inspiringly, in the Alzheimer's disease (AD) mouse model, we observed that AD mice exhibit a ~ 70% reduction in drainage volume of mLVs compared to wild-type mice. With the development of AD, there is be continued decline in mLVs drainage volume. This finding clearly demonstrates that the AD mouse model has impaired CSF drainage. Our study opens up a horizon for understanding the brain's drainage mechanism and dissecting mLVs-associated neurological disorders.

Highly efficient semiconductor modules making controllable parallel microchannels for non-compressible hemorrhages.

Nature makes the most beautiful solution to involuted problems. Among them, the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems, which demonstrate an ingenious evolutionary design. This study develops a mini-thermoelectric semiconductor P-N module to create gradient and parallel channeled hydrogels. The modules decrease quickly the temperature of polymer solution from 20 °C to -20 °C within 5 min. In addition to the exceptional liquid absorption rate, the foams exhibited shape memory mechanics. Our mini device universally makes the inspired structure in such as chitosan, gelatin, alginate and polyvinyl alcohol. Non-compressible hemorrhages are the primary cause of death in emergency. The rapid liquid absorption leads to fast activation of coagulation, which provides an efficient strategy for hemostasis management. We demonstrated this by using our semiconductor modules on collagen-kaolin parallel channel foams with their high porosity (96.43%) and rapid expansion rate (2934%). They absorb liquid with 37.25 times of the own weight, show 46.5-fold liquid absorption speed and 24-fold of blood compared with random porous foams. These superior properties lead to strong hemostatic performance in vitro and in vivo.

Non-invasive modulation of meningeal lymphatics ameliorates ageing and Alzheimer's disease-associated pathology and cognition in mice.

Meningeal lymphatic vessels (mLVs) have been shown to be involved in amyloid beta (Aß) clearance, which is considered as a potential therapeutic target for Alzheimer's disease (AD). In this study, based on the superficial spatial distribution of mLVs, a near-infrared light is employed to modulate lymphatic drainage, significantly improving cognition of both aged and AD (5xFAD and APP/PS1) mice, and alleviating AD-associated pathology by reducing Aß deposition, neuroinflammation and neuronal damage. Furthermore, transmission electron microscopy imaging and RNA sequencing data indicate amelioration of mitochondrial metabolism and cellular junction of meningeal lymphatic endothelial cells (mLECs) by light modulation. These studies collectively suggest that near-infrared light treatment can improve cognitive function by strengthening scavenging ability of mLVs through restoring mLEC function. In conclusion, lymphatic drainage potentiation by light promotes pathological remission and cognitive enhancement in aging and AD mouse models, which offers a potential amelioration strategy for neurodegenerative diseases.

Combined untargeted and targeted lipidomics approaches reveal potential biomarkers in type 2 diabetes mellitus cynomolgus monkeys.

BACKGROUND: The significantly increasing incidence of type 2 diabetes mellitus (T2DM) over the last few decades triggers the demands of T2DM animal models to explore the pathogenesis, prevention, and therapy of the disease. The altered lipid metabolism may play an important role in the pathogenesis and progression of T2DM. However, the characterization of molecular lipid species in fasting serum related to T2DM cynomolgus monkeys is still underrecognized. METHODS: Untargeted and targeted LC-mass spectrometry (MS)/MS-based lipidomics approaches were applied to characterize and compare the fasting serum lipidomic profiles of T2DM cynomolgus monkeys and the healthy controls. RESULTS: Multivariate analysis revealed that 196 and 64 lipid molecules differentially expressed in serum samples using untargeted and targeted lipidomics as the comparison between the disease group and healthy group, respectively. Furthermore, the comparative analysis of differential serum lipid metabolites obtained by untargeted and targeted lipidomics approaches, four common serum lipid species (phosphatidylcholine [18:0_22:4], lysophosphatidylcholine [14:0], phosphatidylethanolamine [PE] [16:1_18:2], and PE [18:0_22:4]) were identified as potential biomarkers and all of which were found to be downregulated. By analyzing the metabolic pathway, glycerophospholipid metabolism was associated with the pathogenesis of T2DM cynomolgus monkeys. CONCLUSION: The study found that four downregulated serum lipid species could serve as novel potential biomarkers of T2DM cynomolgus monkeys. Glycerophospholipid metabolism was filtered out as the potential therapeutic target pathway of T2DM progression. Our results showed that the identified biomarkers may offer a novel tool for tracking disease progression and response to therapeutic interventions.

A novel role for astrocytic fragmented mitochondria in regulating morphine addiction.

Chronic morphine exposure causes the development of addictive behaviors, accompanied by an increase in neuroinflammation in the central nervous system. While previous researches have shown that astrocytes contribute to brain diseases, the role of astrocyte in morphine addiction through induced neuroinflammation remain unexplored. Here we show that morphine-induced inflammation requires the crosstalk among neuron, astrocyte, and microglia. Specifically, astrocytes respond to morphine-induced neuronal activation by increasing glycolytic metabolism. The dysregulation of glycolysis leads to an increased in the generation of mitochondrial reactive oxygen species and causes excessive mitochondrial fragmentation in astrocytes. These fragmented, dysfunctional mitochondria are consequently released into extracellular environment, leading to activation of microglia and release of inflammatory cytokines. We also found that blocking the nicotinamide adenine dinucleotide salvage pathway with FK866 could inhibit astrocytic glycolysis and restore the mitochondrial homeostasis and effectively attenuate neuroinflammatory responses. Importantly, FK866 reversed morphine-induced addictive behaviors in mice. In summary, our findings illustrate an essential role of astrocytic immunometabolism in morphine induced neural and behavioral plasticity, providing a novel insight into the interactions between neurons, astrocytes, and microglia in the brain affected by chronic morphine exposure.

Eschar dissolution and the immunoregulator effect of keratinase on burn wounds.

At present, enzyme debridement preparation has shown a good curative effect on eschar removal of burn wounds. Keratinase has shown great potential in enzymatic debridement because of its good fibrin-degrading ability. In this study, the debridement of keratinase was examined by using a third degree burn wound model in rats. We observed the wound, and keratinase shortened the time of eschar dissolution after debridement. Histopathology and immunofluorescence staining showed that the eschar in the keratinase group became thinner, inflammatory cell infiltration in the wound increased, the fluorescence intensity of the macrophage surface marker CD68 increased, and the CD163/CD86 ratio increased. In bone marrow-derived macrophages (BMDMs), there was no significant difference in the activity of CCK-8 in cells in the keratinase group compared with the control group. The fluorescence intensity of the keratinase group was higher than that of the control group. At 12 h, the cell scratches were obviously closed. The number of migrated Transwell cells increased. Flow cytometry and immunofluorescence analysis showed increased expression of CD206 and Arg-1 and decreased expression of CD86 and iNOS. The gene expression of the Arg-1, iNOS and IL-10 was increased, as shown by qPCR. The secretion of IL-10 was increased and TNF-α was decreased, as shown by ELISA. We concluded that keratinase dissolution of eschar not only has a hydrolytic effect on eschar but may also affect immune regulation to enhance the migration and phagocytosis of macrophages, promote the polarization of macrophages, and further enhance the effect of eschar dissolution. Therefore, keratinase may have good prospects for the debridement of burn wounds.

Characterization of cerebrovascular changes in mice treated with alcohol by photoacoustic imaging.

Alcohol has complex effects on cerebrovascular health. Monitoring the pathology of alcohol induced cerebrovascular changes in vivo is essential for understanding the mechanism and developing potential treatment strategies. Here, photoacoustic imaging was employed to examine cerebrovascular changes in mice under the treatment of alcohol at different doses. By analyzing the association of cerebrovascular structure, hemodynamics, neuronal function and corresponding behavior, we found that alcohol affected brain function and behavior in a dose-dependent manner. Low dose of alcohol increased cerebrovascular blood volume and activated neurons, without addictive behaviors and cerebrovascular structure changes. With the dose increased, cerebrovascular blood volume gradually decreased, triggering obviously progressive effects on the immune microenvironment, cerebrovascular structure and addictive behavior. These findings will provide further insights into the characterization of the biphasic effects of alcohol.

Hydrophobic aerogel-modified hemostatic gauze with thermal management performance.

Current hemostatic agents or dressings are not efficient under extremely hot and cold environments due to deterioration of active ingredients, water evaporation and ice crystal growth. To address these challenges, we engineered a biocompatible hemostatic system with thermoregulatory properties for harsh conditions by combining the asymmetric wetting nano-silica aerogel coated-gauze (AWNSA@G) with a layer-by-layer (LBL) structure. Our AWNSA@G was a dressing with a tunable wettability prepared by spraying the hydrophobic nano-silica aerogel onto the gauze from different distances. The hemostatic time and blood loss of the AWNSA@G were 5.1 and 6.9 times lower than normal gauze in rat's injured femoral artery model. Moreover, the modified gauze was torn off after hemostasis without rebleeding, approximately 23.8 times of peak peeling force lower than normal gauze. For the LBL structure, consisting of the nano-silica aerogel layer and a n-octadecane phase change material layer, in both hot (70 °C) and cold (-27 °C) environments, exhibited dual-functional thermal management and maintained a stable internal temperature. We further verified our composite presented superior blood coagulation effect in extreme environments due to the LBL structure, the pro-coagulant properties of nano-silica aerogel and unidirectional fluid pumping of AWNSA@G. Our work, therefore, shows great hemostasis potential under normal and extreme temperature environments.

Quantitative Proteomic Analysis of Serum Reveals MST1 as a Potential Candidate Biomarker in Spontaneously Diabetic Cynomolgus Monkeys.

The prevalence of type 2 diabetes (T2DM) is increasing globally, creating essential demands for T2DM animal models for the study of disease pathogenesis, prevention, and therapy. A non-human primate model such as cynomolgus monkeys can develop T2DM spontaneously in an age-dependent way similar to humans. In this study, a data-independent acquisition-based quantitative proteomics strategy was employed to investigate the serum proteomic profiles of spontaneously diabetic cynomolgus monkeys compared with healthy controls. The results revealed significant differences in protein abundances. A total of 95 differentially expressed proteins (DEPs) were quantitatively identified in the current study, among which 31 and 64 proteins were significantly upregulated and downregulated, respectively. Bioinformatic analysis revealed that carbohydrate digestion and absorption was the top enriched pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Protein-protein interaction network analysis demonstrated that MST1 was identified as the most connected protein in the network and could be considered as the hub protein. MST1 was significantly and inversely associated with FSG and HbA1c. Furthermore, recent lines of evidence also indicate that MST1 acts as a crucial regulator in regulating hepatic gluconeogenesis to maintain metabolic homeostasis while simultaneously suppressing the inflammatory processes. In conclusion, our study provides novel insights into serum proteome changes in spontaneously diabetic cynomolgus monkeys and points out that the dysregulation of several DEPs may play an important role in the pathogenesis of T2DM.

Preliminary serum and fecal metabolomics study of spontaneously diabetic cynomolgus monkeys based on LC-MS/MS.

BACKGROUND: Using untargeted metabolomics techniques, the goal of the study is to differentially screen serum and feces metabolite profiles of spontaneously diabetic and healthy cynomolgus monkeys, to explore potential serum and fecal biomarkers and analyze affected metabolic pathways. METHODS: We adopted the diagnostic criteria for T2DM recommended by ADA for humans: FSG ≥7.0 mmol/L (126 mg/dl) and HbA1c ≥ 6.5%. The serum and feces samples from three diagnosed spontaneously T2DM cynomolgus monkeys and 11 age-matched healthy controls were enrolled in the study. We employed LC-MS/MS-based untargeted metabolomic methods to reveal the differential metabolite profiles of serum and feces samples between the two groups and to analyze the affected metabolic pathways in MetaboAnalyst 5.0 based on KEGG library. RESULTS: Six and 44 differential metabolites were identified in serum and feces samples, respectively, and the corresponding affected commonly metabolic pathways involved several metabolic ways, such as arginine biosynthesis, pantothenate and CoA biosynthesis, alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, and histidine metabolism. CONCLUSION: The differential potential serum and feces biomarkers obtained from the LC-MS/MS based untargeted metabolomic may help to explain the potential pathophysiological mechanisms of T2DM and offer pivotal information for the early diagnosis and treatment of DM.

Promising Colloidal Rhenium Disulfide Nanosheets: Preparation and Applications for In Vivo Breast Cancer Therapy.

Photothermal therapy (PTT) has become an important therapeutic strategy in the treatment of cancer. However, exploring novel photothermal nanomaterials with satisfactory biocompatibility, high photothermal conversion efficiency, and efficient theranostic outcomes, remains a major challenge for satisfying clinical application. In this study, poly-ethylene glycol modified rhenium disulfide (PEG-ReS2) nanosheets are constructed by a simple-liquid phase exfoliation method. The PEG-ReS2 nanosheets were demonstrated to have good solubility, good biocompatibility, low toxicity, and strong capability of accumulating near-infrared (NIR) photons. Under 808 nm laser irradiation, the PEG-ReS2 nanosheets were found to have an excellent photothermal conversion efficiency (PTCE) of 42%. Moreover, the PEG-ReS2 nanosheets were demonstrated to be ideal photothermal transduction agents (PTAs), which promoted rapid cancer cell death in vitro and efficiently ablated tumors in vivo. Interestingly, the potential utility of up-regulation or down-regulation of miRNAs was proposed to evaluate the therapeutic outcomes of PEG-ReS2 nanosheets. The expression levels of a set of miRNAs in tumor-bearing mice were restored to normal levels after PTT therapy with PEG-ReS2 nanosheets. Both down-regulation miRNAs (miR-125a-5p, miR-34a-5p, miR-132-3p, and miR-148b-3p) and up-regulation miRNAs (miR-133a-3p, miR-200c-5p, miR-9-3p, and miR-150-3p) were suggested to be important clinical biomarkers for evaluating therapeutic outcomes of breast cancer-related PTT. This work highlights the great significance of PEG-ReS2 nanosheets as therapeutic nanoagents for cancer therapy.

Immunoadjuvant Nanoparticles as Trojan Horses for Enhanced Photo-Immunotherapy in the Treatment of Triple-Negative Breast Cancer.

Treatment of triple-negative breast cancer (TNBC) faces great challenges due to high invasiveness and poor prognosis. Therefore, effective treatment methods are urgently needed to control primary tumors and suppress distant tumors. Herein, we employed glycated chitosan (GC), a polysaccharide macromolecular immunoadjuvant, to construct a self-assembly GC@ICG nanoparticle which is accessible to tumor cells for synergistic cancer treatment based on the combination of phototherapy and immunotherapy. In this strategy, the self-associated synthesis of spherical GC@ICG significantly improved the stability of ICG and endowed GC with Trojan Horses in tumor cells to enhance tumor immunogenicity. A bilateral 4T1 tumor-bearing mouse model was established to evaluate the therapeutic outcomes and specific host antitumor immune response. Finally, GC@ICG-based phototherapy can directly eliminate primary tumors and resist the progression of untreated distant tumors. In addition, compared to the treatment of L + GC + ICG, GC@ICG-based phototherapy was evidenced to suppress lung metastasis and enhance infiltration of CD8+ T cells in untreated distant tumors. Therefore, this design shows promise in addressing the challenges of the treatment of TNBC.

Multimodal Imaging-Guided Photothermal Immunotherapy Based on a Versatile NIR-II Aggregation-Induced Emission Luminogen.

Synergistic photothermal immunotherapy has captured great attention owing to the mutually strengthening therapeutic outcomes towards both original tumors and abscopal tumors. Herein, a versatile theranostic agent displaying aggregation-induced emission, namely TPA-BT-DPTQ, was designed and prepared based on benzo[c]thiophene unit as a building block; it can be used for simultaneous fluorescence imaging (FLI) in the second near-infrared (NIR-II) window, photoacoustic imaging (PAI), photothermal imaging (PTI), and thermal eradication of tumors. Further experiments validate that photothermal therapy (PTT) mediated by TPA-BT-DPTQ nanoparticles not only destroys the primary tumor but also enhances immunogenicity for further suppressing the growth of tumors at distant sites. Furthermore, PTT combining a programmed death-ligand 1 (PD-L1) antibody prevents the metastasis and recurrence of cancer by potentiating the effect of immunotherapy.

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.

Subjective cognitive decline-related worries modulate the relationship between global amyloid load and gray matter volume in preclinical Alzheimer's disease.

Subjective cognitive decline (SCD)-related worries are indicative of an increased risk for developing Alzheimer's disease (AD) dementia. However, the influence of SCD-related worries on the relationship between amyloid and gray matter (GM) atrophy remains unknown. A total of 93 SCD participants underwent 18F-florbetapir PET and T1-weighted MRI scans. SCD individuals were classified into amyloid-positive or amyloid-negative groups based on global amyloid uptake. Three-step statistical analyses were performed: (1) partial correlation analysis was conducted to determine whether global amyloid relates to GM volume in amyloid-positive and amyloid-negative groups; (2) linear regression analysis was conducted to determine whether the interaction term (worries × global amyloid) predicts GM volume; and (3) post hoc subgroup linear regression analysis was conducted to determine the association between amyloid and GM volume in the subgroups with and without worries. Age, sex, education and total intracranial volume were adjusted in all models. We found a negative relationship between global amyloid load and GM volume in the right hemisphere (r = 0.441, p = 0.012) and right temporal cortex (r = 0.506, p = 0.003) in the amyloid-positive group. Moreover, in the amyloid-positive group, a significant worries × amyloid interaction effect on GM volume was found in the bilateral hemisphere (right: pinteraction=0.037; left: pinteraction=0.036), left temporal cortex (pinteraction=0.044) and bilateral frontal cortex (right: pinteraction=0.010; left: pinteraction=0.011). Subsequent post hoc analysis revealed a significant amyloid-GM association only in the subgroup with worries but not in the subgroup without worries. In preclinical AD cases, SCD-related worries may occur as a symptom in those cases where amyloid affects GM to a greater extent and may thus represent a high-risk population for future cognitive decline.

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.

Cd-free InP/ZnSeS quantum dots for ultrahigh-resolution imaging of stimulated emission depletion.

Stimulated emission depletion (STED) nanoscopy is a promising super-resolution imaging technique for microstructure imaging; however, the performance of super-resolution techniques critically depends on the properties of the fluorophores (photostable fluorophores) used. In this study, a suitable probe for improving the resolution of STED nanoscopy was investigated. Quantum dots (QDs) typically exhibit good photobleaching resistance characteristics. In comparison with CdSe@ZnS QDs and CsPbBr3 QDs, Cd-free InP/ZnSeS QDs have a smaller size and exhibit an improved photobleaching resistance. Through imaging using InP/ZnSeS QDs, we achieved an ultrahigh resolution of 26.1 nm. Furthermore, we achieved a 31 nm resolution in cell experiments involving InP/ZnSeS QDs. These results indicate that Cd-free InP/ZnSeS QDs have significant potential for application in fluorescent probes for STED nanoscopy.

Noval Dual-Emission Fluorescence Carbon Dots as a Ratiometric Probe for Cu2+ and ClO- Detection.

The use of carbon dots (CDs) with dual emission based on ratiometric fluorescence has been attracting attention in recent times for more accurate ion detection since they help avoid interference from background noise, probe concentration, and complexity. Herein, novel dual-emission nitrogen-doped CDs (NCDs) were prepared by a simple method for Cu2+ and ClO- detection. The NCDs showed excellent anti-interference ability and selectivity for different emissions. In addition, a good linear relationship was observed between the fluorescence intensity (FI) of the NCD solutions in different emissions with Cu2+ (0-90 µM) and ClO- (0-75 µM). The limits of both Cu2+ detection and ClO- were very low, at 17.7 and 11.6 nM, respectively. The NCDs developed herein also showed a good recovery rate in water for Cu2+ and ClO- detection. Hence, they are expected to have a more extensive application prospect in real samples.

Nanoparticle-based approaches to target the lymphatic system for antitumor treatment.

Immunotherapies have been established as safe and efficient modalities for numerous tumor treatments. The lymphatic system, which is an important system, can modulate the immune system via a complex network, which includes lymph nodes, vessels, and lymphocytes. With the deepening understanding of tumor immunology, a plethora of immunotherapies, which include vaccines, photothermal therapy, and photodynamic therapy, have been established for antitumor treatments. However, the deleterious off-target effects and nonspecific targeting of therapeutic agents result in low efficacy of immunotherapy. Fortunately, nanoparticle-based approaches for targeting the lymphatic system afford a unique opportunity to manufacture drugs that can simultaneously tackle both aspects, thereby improving tumor treatments. Over the past decades, great strides have been made in the development of DC vaccines and nanomedicine as antitumor treatments in the field of lymphatic therapeutics and diagnosis. In this review, we summarize the current strategies through which nanoparticle technology has been designed to target the lymphatic system and describe applications of lymphatic imaging for the diagnosis and image-guided surgery of tumor metastasis. Moreover, improvements in the tumor specificity of nanovaccines and medicines, which have been realized through targeting or stimulating the lymphatic system, can provide amplified antitumor immune responses and reduce side effects, thereby promoting the paradigm of antitumor treatment into the clinic to benefit patients.

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.