Biosynthesis of CuTe Nanorods with Large Molar Extinction Coefficients for NIR-II Photoacoustic Imaging.

Photoacoustic imaging (PAI) in the second near-infrared region (NIR-II), due to deeper tissue penetration and a lower background interference, has attracted widespread concern. However, the development of NIR-II nanoprobes with a large molar extinction coefficient and a high photothermal conversion efficiency (PCE) for PAI and photothermal therapy (PTT) is still a big challenge. In this work, the NIR-II CuTe nanorods (NRs) with large molar extinction coefficients ((1.31 ± 0.01) × 108 cm-1·M-1 at 808 nm, (7.00 ± 0.38) × 107 cm-1·M-1 at 1064 nm) and high PCEs (70% at 808 nm, 48% at 1064 nm) were synthesized by living Staphylococcus aureus (S. aureus) cells as biosynthesis factories. Due to the strong light-absorbing and high photothermal conversion ability, the in vitro PA signals of CuTe NRs were about 6 times that of indocyanine green (ICG) in both NIR-I and NIR-II. In addition, CuTe NRs could effectively inhibit tumor growth through PTT. This work provides a new strategy for developing NIR-II probes with large molar extinction coefficients and high PCEs for NIR-II PAI and PTT.

Alterations of DNA methylation profile in peripheral blood of children with simple obesity.

Purpose: To investigate the association between DNA methylation and childhood simple obesity. Methods: Genome-wide analysis of DNA methylation was conducted on peripheral blood samples from 41 children with simple obesity and 31 normal controls to identify differentially methylated sites (DMS). Subsequently, gene functional analysis of differentially methylated genes (DMGs) was carried out. After screening the characteristic DMGs based on specific conditions, the methylated levels of these DMS were evaluated and verified by pyrosequencing. Receiver operating characteristic (ROC) curve analysis assessed the predictive efficacy of corresponding DMGs. Finally, Pearson correlation analysis revealed the correlation between specific DMS and clinical data. Results: The overall DNA methylation level in the obesity group was significantly lower than in normal. A total of 241 DMS were identified. Functional pathway analysis revealed that DMGs were primarily involved in lipid metabolism, carbohydrate metabolism, amino acid metabolism, human diseases, among other pathways. The characteristic DMS within the genes Transcription factor A mitochondrial (TFAM) and Piezo type mechanosensitive ion channel component 1(PIEZO1) were recognized as CpG-cg05831083 and CpG-cg14926485, respectively. Furthermore, the methylation level of CpG-cg05831083 significantly correlated with body mass index (BMI) and vitamin D. Conclusions: Abnormal DNA methylation is closely related to childhood simple obesity. The altered methylation of CpG-cg05831083 and CpG-cg14926485 could potentially serve as biomarkers for childhood simple obesity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-024-00275-w.

Lotus Leaf Extract Alleviates Lipopolysaccharide-Induced Intestinal Injury in Mice by Regulating Oxidative Stress and Inflammation.

Inflammatory bowel disease, a disease featured by intestinal epithelial barrier destruction and dysfunction, has been a constant threat to animal health. The primary objective of this research was to assess the impact of the extract derived from lotus leaves (LLE) on lipopolysaccharide (LPS) induced damage to the intestines in mice, as well as to investigate the fundamental mechanism involved. The LLE was prepared using ultrasonic extraction in this experiment, and the LLE total flavonoid content was 117.02 ± 10.73 mg/g. The LLE had strong antioxidant activity in vitro, as assessed by 2, 2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods. In the vivo experiment, different doses of LLE (50, 100, and 200 mg/kg) were administered for 2 weeks before LPS treatment in mice. The results revealed that LLE alleviates intestinal tissue damage in LPS-induced mice. In the jejunum tissue, LLE significantly upregulated mRNA and protein expression levels of tight junction proteins, such as ZO-1, occludin, and claudin-1, and decreased the contents of the inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. Furthermore, the malondialdehyde and lactate dehydrogenase contents increased by LPS in the liver were significantly reduced after administration of LLE, and the total antioxidant capacity, superoxide dismutase, and reduced glutathione decreased by LPS were remarkably increased by LLE. It was found that LLE could relieve LPS-induced oxidative stress by upregulating mRNA and protein expression of Nrf2 and HO-1 in jejunum tissue. In conclusion, LLE alleviates LPS-induced intestinal damage through regulation of the Nrf2/HO-1 signal pathway to alleviate oxidative stress, reducing inflammatory factors and increasing the expression of tight junction proteins in mice.

Development and testing of a post competency scale for traditional Chinese medicine physicians undergoing standardized training.

Objective: To develop and test a post competency scale for traditional Chinese medicine (TCM) physicians undergoing standardized training to provide an applicable tool for scientific evaluation. Methods: Based on literature analysis, behavioral event interviews, and expert consultations, measurement questions were formulated and the initial scale was designed. A questionnaire survey was conducted from July 2022 to May 2023 among TCM physicians undergoing standardized training in China. The rationality of the scale was confirmed through item purification, factor analysis, and tests of reliability and validity. Results: The post competency scale consisted of three dimensions (TCM fundamentals and research abilities, TCM thinking and skill abilities, and personal traits and communication abilities) with 21 items. Exploratory factor analysis identified three common factors, accounting for a cumulative variance contribution rate of 62.165%. Confirmatory factor analysis demonstrated that the fit indices of the three-factor model fell within a relatively ideal level. The Cronbach's alpha coefficient of the scale was 0.885. Through convergent validity analysis, the standardized loading coefficients of the 21 items were >0.5, and the average extracted variance (AVE) of the three factors was also >0.5. Moreover, the square roots of the AVE values for each dimension exceeded the correlation coefficients between it and the other dimensions. Conclusions: The findings suggest that the post competency scale of TCM physicians undergoing standardized training can provide a reliable scientific basis for training and assessment within China.

Effect of multicomponent intervention on malnutrition in older adults: A multicenter randomized clinical trial.

BACKGROUND & AIMS: Malnutrition is a significant geriatric syndrome (GS) prevalent in older adults and seriously affects patient prognosis and quality of life. We assessed the impact of the multicomponent intervention of health education, dietary advice, and exercise with oral nutritional supplementation (ONS) on nutritional status, body composition, physical functions, and quality of life. METHODS: This multicenter randomized clinical trial (RCT) was performed from April 2021 to April 2022. The intervention lasted for 12 weeks, and 99 older adults with malnutrition or at risk of malnutrition were enrolled in six nursing homes. All participants were randomly assigned to the control (health education plus standard diet plus exercise) or research (health education plus standard diet plus exercise plus ONS) group. The research group consumed ONS (244 kcal, 9.8g protein, and 9.6g fat per time) twice a day between meals. The primary outcomes were changes in the nutritional status and body composition from baseline to 12 weeks. The secondary outcomes were changes in physical function, quality of life and nutritional associated other blood markers. RESULTS: For primary outcomes, after 12 weeks, body weight increased similarly in both treatment arms (time × treatment effect, P > 0.05). There were no between-group differences in body mass index (BMI) or mini nutritional assessment tool-short form (MNA-SF) scores (time × treatment effects, P > 0.05). The MNA-SF score from 11.0 (10.5, 12.0) to 13.0 (11.0, 13.0) in the research group and from 11.0 (10.0, 12.0) to 12.0 (11.0, 13.0) in the control group (both P < 0.05). There were no between-group differences in the skeletal muscle mass index (SMI), fat-free mass index (FFMI), appendicular skeletal muscle mass (ASMM), fat mass (FAT), or leg muscle mass (LMM) (time × treatment effects, P > 0.05). Both groups showed similar and highly significant increases in SMI, FFMI, and LMM after (P < 0.05). The research group showed an increase in fat-free mass (FFM) and ASMM and a decrease in the percent of body fat (PBF) and waist circumference (WC) (P < 0.05). For secondary outcomes, There were no between-group differences in grip strength, short physical performance battery (SPPB), 6-min walking distance (6MWD), activities of daily living (ADL), instrumental activities of daily living (IADL), frailty status (FRAIL), mini-mental state examination (MMSE), Tinetti, geriatric depression scale-15 (GDS-15), or 12-item short form survey (SF-12) (time × treatment effects, P > 0.05). Although there was no significant difference, the 6MWD changed differentially between the two treatment arms during the study period in favor of the research group. Although not significant, SF-12 scores improved after 12 weeks in both groups. No between-group differences were observed in prealbumin (PRE), c-reactive protein (CRP), vitamin D (VIT-D), insulin-like growth factor 1 (IGF-1), alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), insulin, and adiponectin levels (time × treatment effects, P > 0.05). Insulin and adiponectin levels were significantly higher in the control group (P < 0.05). CONCLUSION: The twelve-week multicomponent intervention improved the nutritional status of older people in China at risk of malnutrition. ONS may enhance the effects of exercise on muscle mass. This clinical trial was registered (https://www. CLINICALTRIALS: gov). The trial number is ChiCTR2000040343.

Amelioration of obesity and inflammation by polysaccharide from unripe fruits of raspberry via gut microbiota regulation.

Raspberry, a traditional medicine food homology species, has important benefits in patients with metabolic syndrome. However, the mechanism of raspberry polysaccharides (RP) on obesity remains unclear. In our study, we showed that RP intervention is negatively associated with body weight gain, hyperlipidemia, inflammation, and fat accumulation in obese mice. RP ameliorated HFD-induced gut microbiota dysbiosis, produced short-chain fatty acids, maintained intestinal barrier integrity, and prevented metabolic endotoxemia, manifested by decreased host lipopolysaccharide level, and increased colon expression of tight junction proteins. These effects might be related with driven by a SCFAs-producing bacterium and downregulation of TLR4/NF-κB signaling transduction. Notably, the abundance of Ruminococcaceae_UCG - 014, Lactobacillus taiwanensis, Bifidobacterium pseudolongum, and Turicibacter are markedly correlated with enhanced intestinal barrier function induced by RP treatment. Thus, we believe that RP could be as a potential health supplement or prebiotic for obesity therapy.

Effects of dietary supplementation with Radix Isatidis polysaccharide on egg quality, immune function, and intestinal health in hens.

This study aimed to investigate the effects of supplementing laying hen diets with Radix Isatidis Polysaccharide (RIPS) on egg quality, immune function, and intestinal health. The research was conducted using 288 Hyland Brown hens, which were randomly assigned to four dietary treatments: control (without RIPS), low dose (200 g/t), medium dose (500 g/t), and high dose (1000 g/t) of RIPS. Each dietary treatment was administered to eight replicates of nine hens for nine weeks. The results revealed that RIPS inclusion in diets significantly improved egg quality parameters such as egg shape index, yolk color, haugh unit, and protein height (P < 0.05). Additionally, RIPS supplementation enhanced immune function as evidenced by an alteration in serum biochemical parameters, an increase in the spleen index, and a decrease in the liver index. Further, an evaluation of intestinal health showed that RIPS fortified the intestinal barrier, thus increasing the population of beneficial intestinal bacteria and reducing the abundance of harmful ones. Such mechanisms promoted intestinal health, digestion, and nutrient absorption, ultimately leading to enhanced egg quality. In conclusion, supplementing laying hen diets with RIPS has been demonstrated to improve egg quality by boosting immunity and optimizing intestinal digestion and absorption.

Engineered Selenium/Human Serum Albumin Nanoparticles for Efficient Targeted Treatment of Parkinson's Disease via Oral Gavage.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopamine (DA) neurons in the midbrain substantia nigra pars compacta (SNpc). While existing therapeutic strategies can alleviate PD symptoms, they cannot inhibit DA neuron loss. Herein, a tailor-made human serum albumin (HSA)-based selenium nanosystem (HSA/Se nanoparticles, HSA/Se NPs) to treat PD that can overcome the intestinal epithelial barrier (IEB) and blood-brain barrier (BBB) is described. HSA, a transporter for drug delivery, has superior biological characteristics that make it an ideal potential drug delivery substance. Findings reveal that HSA/Se NPs have lower toxicity and higher efficacy than other selenium species and the ability to overcome the IEB and BBB to enrich DA neurons, which then protect MN9D cells from MPP+-induced neurotoxicity and ameliorate both behavioral deficits and DA neuronal death in MPTP-model mice. Thus, a therapeutic drug delivery system composed of orally gavaged HSA/Se NPs for the treatment of PD is described.

Long-term improvement of sediment in situ restoration and REDOX characteristics by Vallisneria natans coupling with carbon fiber.

China is conducting ecological restoration work in urban water bodies. Under anoxic and anaerobic conditions, pollutants transform and produce odorous and black substances, deteriorating the water quality, which is a significant problem in urban water bodies. Vallisneria natans has received widespread attention for its applications in water treatment and restoration. However, the efficiency by which V. natans reduces water pollution and allows sediment remediation requires further improvement. Therefore, in this study, we investigated the effect of V. natans coupled with carbon fiber on the restoration of water bodies and sediment compared with the control group that grew V. natans without carbon fiber. The oxidation-reduction potential (ORP) was selected as the main evaluation index for the water and sediment. Dissolved oxygen in the water and total organic carbon and total nitrogen (TN) in the sediment were also evaluated. V. natans coupled with carbon fiber significantly increased the ORP; that of surface sediment increased by 50 % and that of the water body increased by 60 % compared with the sediment without any bioremediation. Chemical oxygen demand, total phosphorous, and TN in water decreased by 61.2 %, 22.9 %, and 48.3 %, respectively. These results indicate that planting V. natans with carbon fiber can reduce pollutants in water (including humus) and sediments, effectively improving ORP in water and sediment.

Increased interbrain synchronization and neural efficiency of the frontal cortex to enhance human coordinative behavior: A combined hyper-tES and fNIRS study.

Coordination is crucial for individuals to achieve common goals; however, the causal relationship between coordination behavior and neural activity has not yet been explored. Interbrain synchronization (IBS) and neural efficiency in cortical areas associated with the mirror neuron system (MNS) are considered two potential brain mechanisms. In the present study, we attempted to clarify how the two mechanisms facilitate coordination using hypertranscranial electrical stimulation (hyper-tES). A total of 124 healthy young adults were randomly divided into three groups (the hyper-tACS, hyper-tDCS and sham groups) and underwent modulation of the right inferior frontal gyrus (IFG) during functional near-infrared spectroscopy (fNIRS). Increased IBS of the PFC or neural efficiency of the right IFG (related to the MNS) was accompanied by greater coordination behavior; IBS had longer-lasting effects on behavior. Our findings highlight the importance of IBS and neural efficiency of the frontal cortex for coordination and suggest potential interventions to improve coordination in different temporal windows.

Nanoclay Drug-Delivery System Loading Potassium Iodide Promotes Endocytosis and Targeted Therapy in Anaplastic Thyroid Cancer.

The rapid proliferative biological behavior of primary foci of anaplastic thyroid cancer (ATC) makes it a lethal tumor. According to the specific iodine uptake capacity of thyroid cells and enhanced endocytosis of ATC cells, we designed a kind of nanoclay drug-loading system and showed a promising treatment strategy for ATC. Introducing potassium iodide (KI) improves the homoaggregation of clay nanoparticles and then affects the distribution of nanoparticles in vivo, which makes KI@DOX-KaolinMeOH enriched almost exclusively in thyroid tissue. Simultaneously, the improvement of dispersibility of KI@DOX-KaolinMeOH changes the target uptake of ATC cells by improving the endocytosis and nanoparticle-induced autophagy, which regulate the production of autolysosomes and autophagy-enhanced chemotherapy, eventually contributing to a tumor inhibition rate of more than 90% in the primary foci of ATC. Therefore, this facile strategy to improve the homoaggregation of nanoclay by introducing KI has the potential to become an advanced drug delivery vehicle in ATC treatment.

Protopine Alleviates Dextran Sodium Sulfate-Induced Ulcerative Colitis by Improving Intestinal Barrier Function and Regulating Intestinal Microbiota.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), and its pathogenesis is related to intestinal mucosal barrier damage and gut microbiota imbalance. Protopine (PRO), an isoquinoline alkaloid, is one of the main anti-inflammatory ingredients of traditional Chinese medicine Macleaya cordata(Willd.) R. Br. This study investigated the effects of PRO on the intestinal mucosal barrier and gut microbiota in dextran sodium sulfate (DSS)-induced colitis mice. C57BL/6J mice were treated with 3% DSS in drinking water to induce acute colitis, while PRO was administered orally once daily for 7 days. The results showed that PRO administration significantly alleviated the symptoms of DSS-induced colitis in mice and inhibited the expression of inflammation-related genes. In addition, PRO restored the integrity of the intestinal barrier in colitis mice by restoring colonic mucin secretion and promoting the expression of tight junction proteins. Furthermore, PRO alleviated the DSS-induced gut microbiota dysbiosis by decreasing the abundance of Proteobacteria, Escherichia-Shigella and Enterococcus, as well as enhancing the abundance of beneficial bacteria, such as Firmicutes and Akkermansia. These findings suggested that PRO effectively alleviated DSS-induced ulcerative colitis by suppressing the expression of inflammation-related genes, maintaining the intestinal mucosal barrier and regulating the intestinal microbiota.

[Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers].

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, ß-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

Toxicity and efficacy of green tea catechin derivative-based micellar nanocomplexes for anticancer protein delivery.

Toxicity towards non-tumor cells during anticancer therapy can be reduced by using nanoscale systems for anticancer drug delivery. Usually only the loaded drug has anticancer activity. Recently, micellar nanocomplexes (MNCs) comprising green tea catechin derivatives for the delivery of the anticancer proteins, such as Herceptin, have been developed. Herceptin as well as the MNCs without the drug were effective against HER2/neu-overexpressing human tumor cells and had synergistic anticancer effects in vitro and in vivo. It remained unclear which kinds of negative effects the MNCs had on tumor cells exactly, and which of their components mediated them. Also, it was unclear if MNC has any toxicity effects on the normal cells of vital human organ systems. Herein we examined the effects of Herceptin-MNCs and their individual components on human breast cancer cells and on normal primary human endothelial and kidney proximal tubular cells. We applied a novel in vitro model that predicts nephrotoxicity in humans with high accuracy, as well as high-content screening and microfluidic mono- and co-culture models to thoroughly address effects on various cell types. The results showed that MNCs alone were profoundly toxic for breast cancer cells, and induced apoptosis regardless of HER2/neu expression levels. Apoptosis was induced by both green tea catechin derivatives contained within MNCs. In contrast, MNCs were not toxic for normal human cells, and the probability was low that MNCs would be nephrotoxic in humans. Together, the results supported the hypothesis that green tea catechin derivative-based MNCs could improve efficacy and safety of therapies with anticancer proteins.

Association of maternal methionine synthase reductase gene polymorphisms with the risk of congenital heart disease in offspring: a hospital-based case-control study.

BACKGROUND: Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (MTRR) is one of the key regulatory enzymes in the folate metabolic pathway. This study aimed to comprehensively evaluate the association of single nucleotide polymorphisms (SNPs) in the maternal MTRR gene with CHD risk in offspring. METHODS: A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted. RESULTS: The study showed that maternal MTRR gene polymorphisms at rs1532268 (C/T vs. C/C: aOR = 1.524; T/T vs. C/C: aOR = 3.178), rs1802059 (G/A vs. G/G: aOR = 1.410; A/A vs. G/G: aOR = 3.953), rs2287779 (G/A vs. G/G: aOR = 0.540), rs16879334 (C/G vs. C/C: aOR = 0.454), and rs2303080 (T/A vs. T/T: aOR = 0.546) were associated with the risk of CHD. And seven haplotypes were observed to be associated with the risk of CHD, T-G-A haplotype (OR = 1.298), C-A-C-C (OR = 4.824) and A-G haplotype (OR = 1.751) were associated with increased risk of CHD in offspring; A-A-A (OR = 0.773), T-A-A (OR = 0.557), G-A-C-C (OR = 0.598) and G-C (OR = 0.740) were associated with decreased risk of CHD in offspring. CONCLUSIONS: Maternal MTRR gene polymorphisms were associated with CHD in offspring, and its haplotypes have affected the occurrence of CHD. Furthermore, given the complexity and heterogeneity of CHD, the mechanisms by which these factors influence offspring cardiac development remain unknown, and studies in larger samples in an ethnically diverse population are needed.

Synchronous Interventions of Glucose and Mitochondrial Metabolisms for Antitumor Bioenergetic Therapy.

Hydrogen sulfide (H2 S)-based mitochondrial bioenergetic intervention is an attractive therapeutic modality. However, its therapeutic efficacy is limited owing to metabolic plasticity, which allows tumors to shift their metabolic phenotype between oxidative phosphorylation and glycolysis for energy compensation. To overcome this flexibility, a glycopolymer containing a caged H2 S and hydrogen peroxide (H2 O2 ) dual-donor (1-thio-ß-D-glucose [thioglucose]) is synthesized to wrap glucose oxidase (GOx) for complete depletion of tumorigenic energy sources. The loaded GOx catalyzes the glutathione-activated thioglucose to generate cytotoxic H2 S/H2 O2 , which further induces synergistic defects in mitochondrial function by suppressing cytochrome c oxidase expression and damaging the mitochondrial membrane potential. GOx also blocks glycolysis by depleting endogenous glucose. This synchronous intervention strategy exhibits good anticancer performance, broadening the horizon of antitumor bioenergetic therapy.

Terpyridine-Grafted Nitrogen-Terminal Endowing Cyanine with Metal-Ion-Regulated Photophysical Properties for Cancer Theranostics.

Heptamethine cyanines (Cy7) are one of the most important dyes in bioimaging and phototherapy, but they often suffer from poor photostability or limited photothermal conversion efficiency. Here, a facile molecular engineering approach to regulating the photophysical properties of Cy7 by metal ions is demonstrated. By innovatively modifying the nitrogen with functional groups, a novel terpyridine-grafted nitrogen-terminated Cy7 scaffold (denoted as CydtPy) was synthesized and exhibited tunable photophysical properties when chelating with various metal ions (Mn2+, Fe2+, etc.). In comparison with metal-ion-free PEGylated CydtPy (LET-11), Mn2+-chelated LET-11 (namely, LET-11-Mn) exhibited the increased fluorescence emission intensity, and Fe2+-chelated LET-11 (namely, LET-11-Fe) showed the enhanced photostability with ~2-fold increase in photothermal conversion efficiency. By simply switching the chelated metal ion species, LET-11-Mn or LET-11-Fe could be used for near-infrared fluorescence imaging, magnetic resonance imaging, or photoacoustic imaging. Furthermore, LET-11-Fe displayed superior synergistic efficacy of photothermal therapy and chemodynamic therapy both in vitro and in vivo. This work not only provides a new strategy for regulating the photophysical properties of cyanine dyes but also establishes a versatile nanoplatform for cancer theranostics.

Maximum Emission Peak Over 1500 nm of Organic Assembly for Blood-Brain Barrier-Crossing NIR-IIb Phototheranostics of Orthotopic Glioblastoma.

The development of blood-brain barrier (BBB)-crossing phototheranostic agents in second near-infrared window (NIR-II), especially in the range of 1500-1700 nm (NIR-IIb), affords great opportunities for glioblastoma (GBM) management. Herein, an organic assembly (denoted as LET-12) with the maximum absorption peak at 1400 nm and emission peak at 1512 nm with trailing over 1700 nm through the self-assembly of organic small molecule IR-1064 is designed and subsequently decorated with choline and acetylcholine analogs. The LET-12 can effectively cross BBB through the brain's choline-like receptors-mediated transcytosis and accumulated in tumor tissues, thus achieving fluorescence/photoacoustic (FL/PA) duplex imaging of orthotopic GBM with ≈3.0 mm depth and a superior tumor-to-normal tissue signal ratio (20.93 ± 0.59 for FL imaging and 32.63 ± 1.16 for PA imaging, respectively). Owing to its good photothermal conversion ability, the LET-12 also can serve as a photothermal conversion agent, achieving obvious tumor repression of orthotopic murine GBM model after once treatment. The findings indicate that the LET-12 holds great potential for BBB-crossing NIR-IIb phototheranostics of orthotopic GBM. This self-assembly strategy of organic small molecules opens a new avenue for the construction of NIR-IIb phototheranostics.

Programmably Controllable Delivery of Metastable Ferrous Ions for Multiscale Dynamic Imaging Guided Photothermal Primed Chemodynamic Therapy.

Metallomodulation cell death strategies are extensively investigated for antitumor therapy, such as cuproptosis, ferroptosis, and chemodynamic therapy (CDT). Undoubtedly, the accurate and specific elevation of metal ions levels in cancer cells is key to boosting their therapeutic index. Herein, a programmably controllable delivery system based on croconium dye (Croc)-ferrous ion (Fe2+ ) nanoprobes (CFNPs) is developed for multiscale dynamic imaging guided photothermal primed CDT. The Croc, with kinds of electron-rich iron-chelating groups, can form the Croc-Fe2+ complex with a precise stoichiometry of 1:1 to steadily maintain the valence state of Fe2+ . The CFNPs can achieve pH-responsive visualization and accurate Fe2+ release in cancerous tissues under the coactivation of "dual-key" stimulation of "acidity and near-infrared (NIR) light". The acidic tumor microenvironment actuates NIR fluorescence/photoacoustic imaging and photothermal properties of CFNPs. Sequentially, under exogenous NIR light, the CFNPs enable in vivo accurate visualization of Croc-Fe2+ complex delivery for photothermal primed Fe2+ release, thus achieving CDT of tumors. By leveraging multiscale dynamic imaging technologies, the complicated spatiotemporal release of Fe2+ is sketched in a programmably controllable manner, and the domino effect of tumor pH level, photothermal effect, and CDT is also revealed, endowing customized feedback of the therapeutic panorama within the disease microenvironment.

Precision Delivery of Dual Immune Inhibitors Loaded Nanomodulator to Reverse Immune Suppression for Combinational Photothermal-Immunotherapy.

Although photothermal therapy (PTT) can noninvasively kill tumor cells and exert synergistic immunological effects, the immune responses are usually harmed due to the lack of cytotoxic T cells (CTLs) pre-infiltration and co-existing of intricate immunosuppressive tumor microenvironment (TME), including the programmed cell death ligand 1 (PD-L1)/cluster of differentiation 47 (CD47)/regulatory T cells (Tregs)/M2-macrophages overexpression. Indoleamine 2, 3-dioxygenase inhibitor (NLG919) or bromodomain extra-terminal inhibitor (OTX015) holds great promise to reprogram suppressive TME through different pathways, but their collaborative application remains a formidable challenge because of the poor water solubility and low tumor targeting. To address this challenge, a desirable nanomodulator based on dual immune inhibitors loaded mesoporous polydopamine nanoparticles is designed. This nanomodulator exhibits excellent biocompatibility and water solubility, PTT, and bimodal magnetic resonance/photoacoustic imaging abilities. Owing to enhanced permeability and retention effect and tumor acidic pH-responsiveness, both inhibitors are precisely delivered and locally released at tumor sites. Such a nanomodulator significantly reverses the immune suppression of PD-L1/CD47/Tregs, promotes the activation of CTLs, regulates M2-macrophages polarization, and further boosts combined therapeutic efficacy, inducing a strong immunological memory. Taken together, the nanomodulator provides a practical approach for combinational photothermal-immunotherapy, which may be further broadened to other "immune cold" tumors.