Novel 131-iodine labeled and ultrasound-responsive nitric oxide and reactive oxygen species controlled released nanoplatform for synergistic sonodynamic/nitric oxide/chemodynamic/radionuclide therapy.

Nitric oxide (NO) and reactive oxygen species (ROS) embody excellent potential in cancer therapy. However, as a small molecule, their targeted delivery and precise, controllable release are urgently needed to achieve accurate cancer therapy. In this paper, a novel US-responsive bifunctional molecule (SD) and hyaluronic acid-modified MnO2 nanocarrier was developed, and a US-responsive NO and ROS controlled released nanoplatform was constructed. US can trigger SD to release ROS and NO simultaneously at the tumor site. Thus, SD served as acoustic sensitizer for sonodynamic therapy and NO donor for gas therapy. In the tumor microenvironment, the MnO2 nanocarrier can effectively deplete the highly expressed GSH, and the released Mn2+ can make H2O2 to produce .OH by Fenton-like reaction, which exhibited a strong chemodynamic effect. The high concentration of ROS and NO in cancer cell can induce cancer cell apoptosis ultimately. In addition, toxic ONOO-, which was generated by the reaction of NO and ROS, can effectively cause mitochondrial dysfunction, which induced the apoptosis of tumor cells. The 131I was labeled on the nanoplatform, which exhibited internal radiation therapy for tumor therapy. In -vitro and -vivo experiments showed that the nanoplatform has enhanced biocompatibility, and efficient anti-tumor potential, and it achieves synergistic sonodynamic/NO/chemodynamic/radionuclide therapy for cancer.

Synthesis and evaluation of a 68Ga-labeled spermine derivative for tumor PET imaging.

BACKGROUND: The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([68Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor. RESULTS: The radiochemical yield of [68Ga]Ga-NOTA-Spermine was determined to be 64-69 %, demonstrating exceptional stability and radiochemical purity (>98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [68Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [68Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [68Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71. CONCLUSION: These results suggest that [68Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.

Effects of postoperative antioxidants on the salivary glands in patients with thyroid cancer undergoing radioactive iodine-131 treatment.

OBJECTIVE: This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I). METHODS: A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment. RESULTS: Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05). CONCLUSION: During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.

Overall survival and short-term efficacy analysis of cervical squamous cell carcinoma with skeletal muscle and 18F-FDG PET/CT parameters.

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can provide tumor biological metabolism and skeletal muscle composition information. The aim of this study was to evaluate overall survival (OS) and short-term efficacy of cervical squamous cell carcinoma combining tumor biological metabolism and skeletal muscle composition parameters. Eighty two patients with cervical squamous cell carcinoma were included in the study, who received 18F-FDG PET/CT scans before treatment. Clinical characteristics, tumor biological metabolism parameters [standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis, heterogeneity of tumors, etc.] and body composition parameters were recorded. The survival analysis of cervical squamous cell carcinoma patients was performed by univariate and multivariate analysis. A combined model included clinical indicators, tumor metabolism parameters and sarcopenia was constructed to evaluate OS of patients. According to the Response Evaluation Criteria in Solid Tumours version 1.1, the relationship between sarcopenia with tumor metabolism parameters and short-term efficacy was investigated in subgroup. The results indicate that sarcopenia and high value of the sum of MTV of lesions and metastases (MTVtotal) were poor prognostic factors in patients with cervical squamous cell carcinoma. The combination of sarcopenia, MTVtotal and clinical factors provided an improved prediction of OS especially in the long term after treatment. Nutritional status of the patients and tumor metabolism may not affect the short-term efficacy of chemoradiotherapy in cervical squamous cell carcinoma patients.

Predictive value of 18F-FDG PET/CT radiomics for EGFR mutation status in non-small cell lung cancer: a systematic review and meta-analysis.

Objective: This study aimed to evaluate the value of 18F-FDG PET/CT radiomics in predicting EGFR gene mutations in non-small cell lung cancer by meta-analysis. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and CNKI databases were searched from the earliest available date to June 30, 2023. The meta-analysis was performed using the Stata 15.0 software. The methodological quality and risk of bias of included studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 and Radiomics Quality Score criteria. The possible causes of heterogeneity were analyzed by meta-regression. Results: A total of 17 studies involving 3763 non-small cell lung cancer patients were finally included. We analyzed 17 training cohorts and 10 validation cohorts independently. Within the training cohort, the application of 18F-FDG PET/CT radiomics in predicting EGFR mutations in NSCLC demonstrated a sensitivity of 0.76 (95% CI: 0.70-0.81) and a specificity of 0.78 (95% CI: 0.74-0.82), accompanied by a positive likelihood ratio of 3.5 (95% CI:3.0-4.2), a negative likelihood ratio of 0.31 (95% CI: 0.24-0.39), a diagnostic odds ratio of 11.0 (95% CI: 8.0-16.0), and an area under the curve (AUC) of 0.84 (95% CI: 0.80-0.87). In the validation cohort, the values included a sensitivity of 0.76 (95% CI: 0.67-0.83), a specificity of 0.75 (95% CI: 0.68-0.80), a positive likelihood ratio of 3.0 (95% CI:2.4-3.8), a negative likelihood ratio of 0.32 (95% CI: 0.24-0.44), a diagnostic odds ratio of 9 (95% CI: 6-15), and an AUC of 0.82 (95% CI: 0.78-0.85). The average Radiomics Quality Score (RQS) across studies was 10.47 ± 4.72. Meta-regression analysis identifies the application of deep learning and regions as sources of heterogeneity. Conclusion: 18F-FDG PET/CT radiomics may be useful in predicting mutation status of the EGFR gene in non-small cell lung cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022385364.

Manipulating HGF signaling reshapes the cirrhotic liver niche and fills a therapeutic gap in regeneration mediated by transplanted stem cells.

Long-term stem cell survival in the cirrhotic liver niche to maintain therapeutic efficacy has not been achieved. In a well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhosis animal model, we previously showed that liver-resident stem/progenitor cells (MLpvNG2+ cells) or immune cells have improved survival in the fibrotic liver environment but died via apoptosis in the cirrhotic liver environment, and increased levels of hepatocyte growth factor (HGF) mediated this cell death. We tested the hypothesis that inhibiting HGF signaling during the cirrhotic phase could keep the cells alive. We used adeno-associated virus (AAV) vectors designed to silence the c-Met (HGF-only receptor) gene or a neutralizing antibody (anti-cMet-Ab) to block the c-Met protein in the DEN-induced liver cirrhosis mouse model transplanted with MLpvNG2+ cells between weeks 6 and 7 after DEN administration, which is the junction of liver fibrosis and cirrhosis at the site where most intrahepatic stem cells move toward apoptosis. After 4 weeks of treatment, the transplanted MLpvNG2+ cells survived better in c-Met-deficient mice than in wild-type mice, and cell activity was similar to that of the mice that received MLpvNG2+ cells at 5 weeks after DEN administration (liver fibrosis phase when most of these cells proliferated). Mechanistically, a lack of c-Met signaling remodeled the cirrhotic environment, which favored transplanted MLpvNG2+ cell expansion to differentiation into mature hepatocytes and initiate endogenous regeneration by promoting mature host hepatocyte generation and mediating functional improvements. Therapeutically, c-Met-mediated regeneration can be mimicked by anti-cMet-Ab to interfere functions, which is a potential drug for cell-based treatment of liver fibrosis/cirrhosis.

Comparative effects of hepatocyte growth factor and tacrolimus on acute liver allograft early tolerance.

Allostimulated CD8+ T cells (aCD8+ T cells), as the main mediators of acute liver rejection (ARJ), are hyposensitive to apoptosis due to the inactivation of death receptor FAS-mediated pathways and fail to allow tolerance induction, eventually leading to acute graft rejection. Although tacrolimus (FK506), the most commonly used immunosuppressant (IS) in the clinic, allows tolerance induction, its use is limited because its target immune cells are unknown and it is associated with increased incidences of malignancy, infection, and nephrotoxicity, which substantially impact long-term liver transplantation (LTx) outcomes. The dark agouti (DA)-to-Lewis rat LTx model is a well-known ARJ model and was hence chosen for the present study. We show that both hepatocyte growth factor (HGF) (cHGF, containing the main form of promoting HGF production) and recombinant HGF (h-rHGF) exert immunoregulatory effects mainly on allogeneic aCD8+ T cell suppression through FAS-mediated apoptotic pathways by inhibiting cMet to FAS antagonism and Fas trimerization, leading to acute tolerance induction. We also showed that such inhibition can be abrogated by treatment with neutralizing antibodies against cMet (HGF-only receptor). In contrast, we did not observe these effects in rats treated with FK506. However, we observed that the effect of anti-rejection by FK506 was mainly on allostimulated CD4+ T cell (aCD4+ T cell) suppression and regulatory T cell (Treg) promotion, in contrast to the mechanism of HGF. In addition, the protective mechanism of HGF in FK506-mediated nephrotoxicity was addressed. Therefore, HGF as a tolerance inducer, whether used in combination with FK506 or as monotherapy, may have good clinical value. Additional roles of these T-cell subpopulations in other biological systems and studies in these fields will also be meaningful.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Comparative study of the quantitative accuracy of oncological PET imaging based on deep learning methods.

Background: [18F] Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an important tool for tumor assessment. Shortening scanning time and reducing the amount of radioactive tracer remain the most difficult challenges. Deep learning methods have provided powerful solutions, thus making it important to choose an appropriate neural network architecture. Methods: A total of 311 tumor patients who underwent 18F-FDG PET/CT were retrospectively collected. The PET collection time was 3 min/bed. The first 15 and 30 s of each bed collection time were selected to simulate low-dose collection, and the pre-90s was used as the clinical standard protocol. Low-dose PET was used as input, convolutional neural network (CNN, 3D Unet as representative) and generative adversarial network (GAN, P2P as representative) were used to predict the full-dose images. The image visual scores, noise levels and quantitative parameters of tumor tissue were compared. Results: There was high consistency in image quality scores among all groups [Kappa =0.719, 95% confidence interval (CI): 0.697-0.741, P<0.001]. There were 264 cases (3D Unet-15s), 311 cases (3D Unet-30s), 89 cases (P2P-15s) and 247 cases (P2P-30s) with image quality score ≥3, respectively. There was significant difference in the score composition among all groups (χ2=1,325.46, P<0.001). Both deep learning models reduced the standard deviation (SD) of background, and increased the signal-to-noise ratio (SNR). When 8%PET images were used as input, P2P and 3D Unet had similar enhancement effect on SNR of tumor lesions, but 3D Unet could significantly improve the contrast-noise ratio (CNR) (P<0.05). There was no significant difference in SUVmean of tumor lesions compared with s-PET group (P>0.05). When 17%PET image was used as input, SNR, CNR and SUVmax of tumor lesion of 3D Unet group had no statistical difference with those of s-PET group (P>0.05). Conclusions: Both GAN and CNN can suppress image noise to varying degrees and improve image quality. However, when 3D Unet reduces the noise of tumor lesions, it can improve the CNR of tumor lesions. Moreover, quantitative parameters of tumor tissue are similar to those under the standard acquisition protocol, which can meet the needs of clinical diagnosis.

CMR validation of left ventricular volumes and ejection fraction measured by the IQ-SPECT system in patients with small heart size.

BACKGROUND: The IQ-SPECT system is equipped with multifocal collimators and uses ordered-subset conjugate gradient minimization (OSCGM) as its reconstruction algorithm, achieving a shorter acquisition time than conventional SPECT. Left ventricular ejection fraction (LVEF) is overestimated by conventional SPECT in patients with small heart size. In this study, we compared IQ-SPECT with conventional SPECT and cardiovascular magnetic resonance (CMR) for the estimation of LVEF in patients with small hearts (males: EDV ≤ 60 ml, ESV ≤ 25 ml; females: EDV ≤ 45 ml, ESV ≤ 20 ml). METHODS: The study consisted of 49 consecutive patients (20 normal and 29 with small heart size) undergoing gated myocardial perfusion imaging (GMPI) with a 99mTc-labelled agent during stress or rest to assess the risk of coronary artery disease (CAD). The data were reconstructed using filtered back-projection (FBP) for conventional SPECT and OSCGM for IQ-SPECT. ESV, EDV, and LVEF were calculated using quantitative gated SPECT (QGS). To determine the optimal ordered-subset reconstruction parameters, we compared the LVEF from SPECT to the corresponding measurement from CMR. RESULTS: EDV, ESV, and LVEF values obtained from IQ-SPECT and conventional SPECT showed that the results of these two forms of SPECT were significantly correlated, although the EDV and ESV obtained by IQ-SPECT were higher than those obtained by conventional SPECT. IQ-SPECT yielded lower LVEF measurements than conventional SPECT (normal heart size: 50.6 ± 4.3% vs. 73.4 ± 8.4%, P = 0.002; small heart size: 62.1 ± 7.8% vs. 75.0 ± 11.4%, P < 0.001). There were no significant differences in LVEF measurements made by IQ-SPECT and CMR (normal heart size: 50.6 ± 4.3% vs. 53.2 ± 5.8%, P > 0.05; small heart size: 62.1 ± 7.8% vs. 64.6 ± 8.8%, P > 0.05). Five subsets (S) and 12 iterations (I) did not differ significantly in LVEF between CMR and IQ-SPECT for patients with small hearts (64.6 ± 8.8% vs. 62.1 ± 7.8%, P = 0.120), while 3 S and 10 I were the best parameters for patients with normal heart size (50.6 ± 4.3% vs. 53.1 ± 5.8%, P = 0.117). CONCLUSION: With CMR as the standard, IQ-SPECT yields more reliable LVEF values than conventional SPECT for populations with small heart size. The best reconstruction parameters from IQ-SPECT were 5 S and 12 I for patients with small hearts.

Accurate Visualization of Metabolic Aberrations in Cancer Cells by Temperature Mapping with Quantum Coherence Modulation Microscopy.

Specific metabolic aberrations of cancer cells rapidly generate energy with a minuscule but detectable temperature variation, which is a typical characteristic providing insight into cancer pathogenesis. However, to date, intracellular temperature mapping of cancer cell metabolism with high temporal and spatial resolution has not been realized. In this study, we mapped and monitored in real-time the intracellular temperature variations of mitochondria and cytoplasm at a subcellular scale via a single-molecule coherent modulation microscopy coupling targeted molecule labeling technique. According to the variation of the decoherence processes of targeted molecules as a function of intracellular temperature, we achieved a high temperature resolution (<0.1 K) and proved that this technique could eliminate interference from fluorescence intensity disturbance and external pH change. Furthermore, we showed a positive correlation between the determined temperature and the adenosine triphosphate production rate of mitochondrial metabolism in combination with a cell energy metabolic analyzer. This technology enables accurate real-time temporal and spatial visualization of cancer metabolism and establishes diagnoses and therapies for cancer.

Radionuclide labeled nanocarrier for imaging guided combined radionuclide, sonodynamic, and photothermal therapy of pancreatic tumours.

Radionuclide therapy (RNT) is an effective method for the clinical precise treatment of cancer. However, the uneven dose distribution and rapid metabolism of nuclides limit the effective killing of tumors. To overcome the limitations of radionuclide therapeutic approaches, combining different therapeutic strategies to treat cancer has manifested great promise in basic and clinical research. Here, a new combination therapy strategy was developed to combine radionuclide therapy, sonodynamic therapy and photothermal therapy (RNT-SDT-PTT) under radionuclide imaging guided achieve highly effective combination therapy. We prepared a polydopamine-modified Au nanostar (AN), then loaded with the acoustic sensitizer protoporphyrin (IX) and labeled with diagnostic (99mTc) or therapeutic (131I) radionuclides (131I/99mTc-AN@D/IX) for the precise diagnosis and treatment of pancreatic cancer. After intratumor administration, single photon emission computed tomography imaging showed that the nanocarriers were mostly retained in the tumor compared to free radionuclide. As well as using near-infrared light to trigger PTT and ultrasound with high penetration depth to activate IX to generate reactive oxygen species achieved SDT of tumor. The ultimate significantly improved the inhibitory effects by the RNT-SDT-PTT combined therapy for pancreatic cancer. Therefore, this study proposes an effective radionuclide combination therapy regimen consisting of three widely used treatments, offering promising prospects for the future of oncology.

A new 68Ga-labeled ornithine derivative for PET imaging of ornithine metabolism in tumors.

Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) for the synthesis of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel 68Ga-labeled ornithine derivative ([68Ga]Ga-NOTA-Orn). The synthesis time of [68Ga]Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45-50% (uncorrected), and the radiochemical purity was > 98%. [68Ga]Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of [68Ga]Ga-NOTA-Orn was similar to that of L-ornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micro-positron emission tomography (Micro-PET) imaging studies showed that [68Ga]Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that [68Ga]Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.

Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1).

BACKGROUND: [18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging. METHODS: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners. RESULTS: This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies. CONCLUSION: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging. KEY POINTS: • [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.

Targeted chemo-photodynamic therapy toward esophageal cancer by GSH-sensitive theranostic nanoplatform.

As the sixth leading cause of cancer death, esophageal cancer is threatening the life of people worldwide. Traditional treatments, such as surgery, chemotherapy, radiotherapy, are facing always augmented challenges including invasion, multidrug resistance (MDR), off-target toxicity. Chemo & Photodynamic synergistic therapy represents one promising strategy for improved treatment efficiency. But it is still hindered by the lack of tumor targeting, deleterious side effects, and unfavorable microenvironment for photodynamic therapy (PDT). To overcome those obstacles, one theranostic nano-assambly drug, GCDs-Ce6/Pt-EGF, was designed and fabricated. Green fluorescence carbon dots (GCDs) with the excellent optical properties, modifiability and low toxicity were prepared as drug carrier. Epidermal growth factor (EGF) was conjugated to the nano-assembly to realize tumor specific targeting. Chlorin e6 (Ce6) in the presence of laser irradiation achieved PDT by generating proapoptosis reactive oxygen species (ROS). Moreover, Ce6 incorporated into GCDs endowed the nano-assambly imaging ability and facilitate image-guided therapy. Pt(IV), cisplatin prodrug, in the nano-assambly depleted the glutathione (GSH) of tumor microenvironment when it was reduced to cytotoxicity Pt(II). Compared with single treatment, GCDs-Ce6/Pt-EGF exhibited enhanced tumor cell killing capacity and better biosafety in vitro and in vivo, especially for EGFR bearing tumor. It paved ways for developing novel theranostic agent to be potentially applied in clinic.

Differential distribution and prognostic value of CD4+ T cell subsets before and after radioactive iodine therapy in differentiated thyroid cancer with varied curative outcomes.

Differentiated thyroid cancer is the most frequently diagnosed endocrine tumor. While differentiated thyroid cancers often respond to initial treatment, little is known about the differences in circulating immune cells amongst patients who respond differently. A prospective study of 39 patients with differentiated thyroid cancer was conducted. Serum thyroglobulin levels and thyroid and immunological functions were tested before and after radioactive iodine treatment (RAIT). Efficacy assessments were performed 6 to 12 months after radioactive iodine treatment. Most patients showed an excellent response to radioactive iodine treatment. Before radioactive iodine treatment, the excellent response group had considerably fewer circulating CD4+ T cell subsets than the non-excellent response group. Both the excellent response and non-excellent response groups had considerably lower circulating CD4+ T lymphocyte subsets 30 days after radioactive iodine treatment, but those of the excellent response group were still lower than those of the non-excellent response group. All circulating CD4+ T cell subsets in the excellent response group rose by varying degrees by the 90th day, but only Treg cell amounts increased in the non-excellent response group. Interestingly, in the non-excellent response group, we noticed a steady drop in Th1 cells. However, the bulk of circulating CD4+ T cell subsets between the two groups did not differ appreciably by the 90th day. Finally, we discovered that CD4+ T cell subsets had strong predictive potential, and we thus developed high-predictive-performance models that deliver more dependable prognostic information. In conclusion, in individuals with differentiated thyroid cancer, there is great variation in circulating immune cells, resulting in distinct treatment outcomes. Low absolute CD4+ T cell counts is linked to improved clinical outcomes as well as stronger adaptive and resilience capacities.

Construction of mitochondria targeted and FRET based ratiometric sensing nanoplatform for sulfur dioxide accurate detection in vitro and in vivo.

Sulfur dioxide (SO2) is a key molecule in organisms that is involved in the regulation of different physiological procedures. Aberrant SO2 causes a variety of diseases, such as cancer and neurodegeneration. Thus, sensitive and selective detection of SO2 is of great importance. Based on the Förster resonance energy transfer (FRET) between green fluorescence carbon dots (GCDs) donor and amide-linked near-infrared fluorescence emissive organic small molecular dye (CDDBT) acceptor, one ratiometric fluorescent nano platform, Mito-GCDs-CDDBT for mitochondria SO2 sensing was constructed. In this FRET sensing system, CDDBT served as the receptor for SO2, and the presence of SO2 enhanced GCDs green fluorescence signal and quenched CDDBT near-infrared fluorescence signal due to the disruption of FRET. Mito-GCDs-CDDBT could sensitively detect SO2 with a detection limit of as low as 0.701 µM. Meanwhile, Mito-GCDs-CDDBT achieved fluorescence imaging to measure the response of cellular exogenous and endogenous SO2 with remarkable mitochondrial targeting. Moreover, Mito-GCDs-CDDBT also realized SO2 sensing in vivo including zebrafish and mice. The as-prepared versatile nanoplatform displayed several advantages, such as mitochondria targeting, FRET-based sensitive detection, and sensing capabilities in biological milieu. Potentially, it could be applied in the diagnostics of SO2 involved diseases.

MRI/fluorescence dual-mode probe: its simple preparation method and imaging application in vitro.

Superparamagnetic nanoparticles have been widely used as contrast agents in magnetic resonance imaging (MRI). The combined use of multiple imaging modes can provide more accurate information for clinical diagnosis. In this paper, a MRI/fluorescence dual-mode imaging contrast agent was developed by a simple method. The method is to make the fluorescent carbon quantum dots (CDs) adsorbed on the surface of the magnetic composite with pore structure by ultrasonic dispersion. Replacing the traditional methods such as chemical bonding, the fluorescent material is coated on the surface of the composite material. The synthesized composite materials were characterized by the transmission electron microscopy method (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and vibration sample magnetometer (VSM). The results of TEM, FTIR and XPS showed that CDs were successfully coated on the surface of C60@Fe3O4 magnetic composite. The VSM results show that the composite material still maintains superparamagnetism. The cytotoxicity of the material on SMMC-7721 liver cancer cells was detected by the MTT method, and the biocompatibility of the material was verified. By observing the fluorescence distribution in the cell, it is proved that the composite material successfully enters the cell and produces fluorescence. Finally, through the analysis of T2-weighted imaging, it is found that the addition of materials results in an enhanced dark contrast compared to control cells. Therefore, the composite nanomaterials synthesized in this paper can be used as MRI/fluorescence dual-mode imaging contrast agents.