Association of genetic polymorphisms with mercapturic acids in the urine of young healthy subjects before and after exposure to outdoor air pollution.

We aimed to identify the relationship between variations in metabolic genes and human urinary changes in mercapturic acids (MAs), including CEMA, HMPMA, SPMA, HPMA and HEMA, before and after air pollution exposure. Genotype detection for 47 relevant single nucleotide polymorphisms (SNPs) collected by literature research was performed. Five MAs expression levels in the urinary samples of 50 young healthy individuals with short-term exposure to clean, polluted and purified air at five time points were detected by targeted online solid-phase extraction liquid chromatography tandem mass spectrometry (SPE-LC-MS/MS), followed with associations of SNPs with MAs changes. Difference in MAs between polluted and clean/purified air was significantly associated with 21 SNPs mapped into 9 genes. Five SNPs in GSTP1 showed the most prominent association with the changes in SPMA expression, indicating that those SNPs in GSTP1 and SPMA might serve as biomarkers for susceptibility and the prognosis of lung cancer.

Different transcriptome profiles between human retinoblastoma Y79 cells and an etoposide-resistant subline reveal a chemoresistance mechanism.

BACKGROUND: Retinoblastoma (RB) is the most frequent pediatric retinal tumor. In the present study, to elucidate chemoresistance mechanisms and identify potential biomarkers in RB, we utilized RNA sequencing (RNAseq) technological platforms to reveal transcriptome profiles and identify any differentially expressed genes (DEGs) between an etoposide drug-resistant subline (Y79/EDR) and parental Y79 cells. METHODS: To test whether Y79/EDR cells showed resistance to antineoplastic agents for RB, we treated the cells with etoposide, carboplatin and vincristine and analyzed them with a Cell Counting Kit-8 (CCK-8). Y79/EDR and parental Y79 cells were used for RNAseq and bioinformatics analysis to enable a genome-wide review of DEGs between the two lines using the DESeq R package (1.10.1). Then, DEG enrichment in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was analyzed with KOBAS software. Next, real-time quantitative reverse transcription polymerase chain reaction (real time QRT-PCR) and cytotoxicity assays were performed to experimentally and functionally validate the identified candidate biomarkers. RESULTS: Y79/EDR cells showed resistance to etoposide, carboplatin and vincristine at different concentrations. In total, 524 transcripts were differentially expressed in Y79/EDR cells based on analysis of fragments per kilobase of transcript per million fragments mapped (FPKM); among these, 57 genes were downregulated and 467 genes were upregulated in Y79/EDR cells compared to parental Y79 cells. We selected candidate DEGs, including ARHGAP9, HIST1H4H, RELN, DDIT4, HK2, STC1 and PFKFB4, for mRNA expression validation with real time QRT-PCR assays and found that the expression levels determined by real time QRT-PCR were consistent with the RNAseq data. Further studies involving downregulation of ARHGAP9 with a specific siRNA showed that ARHGAP9 altered the cellular sensitivity of Y79 cells to etoposide and carboplatin. CONCLUSION: Our initial findings provided a genomic view of the transcription profiles of etoposide-induced acquired resistance in RB. Follow-up studies indicated that ARHGAP9 might be a chemoresistance biomarker in RB, providing insight into potential therapeutic targets for overcoming acquired chemoresistance in RB. These findings can aid in understanding and overcoming chemoresistance during treatment of RB in the clinic.

To reduce premature drug release while ensuring burst intracellular drug release of solid lipid nanoparticle-based drug delivery system with clathrin modification.

Nanoscale drug delivery system (NDDS) with slow premature drug release (PDR) while ensuring burst intracellular drug release (BIDR) is becoming a hot point in NDDS-based nanomedicine. Here we used clathrin to modify a solid lipid nanoparticle (SLN)-based NDDS of salinomycin (SLN-SAL) to prepare NDDS with reduced PDR while ensuring BIDR. Drug-release-kinetic experiments revealed that clathrin modified SLN-SAL (CMSLN-SAL) reduced PDR while ensured BIDR of its prototype NDDS, SLN-SAL. Mechanism experiments revealed that clathrin modification reduced PDR of SLN-SAL through increasing the mechanical strength of SLN-SAL and ensured BIDR of SLN-SAL through lipid membrane fusion after its clathrin shell was de-polymerized by a cytoplasm enzyme, HSC70. In addition, CMSLN-SAL had significantly higher intracellular uptake and stronger inhibitive effects on cancer cells than that of SLN-SAL. These results demonstrated that clathrin modification is an effective way to reduce PDR while ensuring BIDR and increasing the anticancer effects of SLN-based NDDS.

A study on the improvement in the ability of endoscopists to diagnose gastric neoplasms using an artificial intelligence system.

Background: Artificial intelligence-assisted gastroscopy (AIAG) based on deep learning has been validated in various scenarios, but there is a lack of studies regarding diagnosing neoplasms under white light endoscopy. This study explored the potential role of AIAG systems in enhancing the ability of endoscopists to diagnose gastric tumor lesions under white light. Methods: A total of 251 patients with complete pathological information regarding electronic gastroscopy, biopsy, or ESD surgery in Xi'an Gaoxin Hospital were retrospectively collected and comprised 64 patients with neoplasm lesions (excluding advanced cancer) and 187 patients with non-neoplasm lesions. The diagnosis competence of endoscopists with intermediate experience and experts was compared for gastric neoplasms with or without the assistance of AIAG, which was developed based on ResNet-50. Results: For the 251 patients with difficult clinical diagnoses included in the study, compared with endoscopists with intermediate experience, AIAG's diagnostic competence was much higher, with a sensitivity of 79.69% (79.69% vs. 72.50%, p = 0.012) and a specificity of 73.26% (73.26% vs. 52.62%, p < 0.001). With the help of AIAG, the endoscopists with intermediate experience (<8 years) demonstrated a relatively higher specificity (59.79% vs. 52.62%, p < 0.001). Experts (≥8 years) had similar results with or without AI assistance (with AI vs. without AI; sensitivities, 70.31% vs. 67.81%, p = 0.358; specificities, 83.85% vs. 85.88%, p = 0.116). Conclusion: With the assistance of artificial intelligence (AI) systems, the ability of endoscopists with intermediate experience to diagnose gastric neoplasms is significantly improved, but AI systems have little effect on experts.

Comparative study on genomic and epigenomic profiles of retinoblastoma or tuberous sclerosis complex via nanopore sequencing and a joint screening framework.

Recurrence and extraocular metastasis in advanced intraocular retinoblastoma (RB) are still major obstacles for successful treatment of Chinese children. Tuberous sclerosis complex (TSC) is a very rare, multisystemic genetic disorder characterized by hamartomatous growth. In this study, we aimed to compare genomic and epigenomic profiles with human RB or TSC using recently developed nanopore sequencing, and to identify disease-associated variations or genes. Peripheral blood samples were collected from either RB or RB/TSC patients plus their normal siblings, followed by nanopore sequencing and identification of disease-specific structural variations (SVs) and differentially methylated regions (DMRs) by a systematic biology strategy named as multiomics-based joint screening framework. In total, 316 RB- and 1295 TSC-unique SVs were identified, as well as 1072 RB- and 1114 TSC-associated DMRs, respectively. We eventually identified 6 key genes for RB for further functional validation. Knockdown of CDK19 with specific siRNAs significantly inhibited Y79 cellular proliferation and increased sensitivity to carboplatin, whereas downregulation of AHNAK2 promoted the cell growth as well as drug resistance. Those two genes might serve as potential diagnostic markers or therapeutic targets of RB. The systematic biology strategy combined with functional validation might be an effective approach for rare pediatric malignances with limited samples and challenging collection process.

Activated Carbon nanoparticles Loaded with Metformin for Effective Against Hepatocellular Cancer Stem Cells.

Introduction: Hepatocellular cancer stem cells (CSCs) play crucial roles in hepatocellular cancer initiation, development, relapse, and metastasis. Therefore, eradication of this cell population is a primary objective in hepatocellular cancer therapy. We prepared a nanodrug delivery system with activated carbon nanoparticles (ACNP) as carriers and metformin (MET) as drug (ACNP-MET), which was able to selectively eliminate hepatocellular CSCs and thereby increase the effects of MET on hepatocellular cancers. Methods: ACNP were prepared by ball milling and deposition in distilled water. Suspension of ACNP and MET was mixed and the best ratio of ACNP and MET was determined based on the isothermal adsorption formula. Hepatocellular CSCs were identified as CD133+ cells and cultured in serum-free medium. We investigated the effects of ACNP-MET on hepatocellular CSCs, including the inhibitory effects, the targeting efficiency, self-renewal capacity, and the sphere-forming capacity of hepatocellular CSCs. Next, we evaluated the therapeutic efficacy of ACNP-MET by using in vivo relapsed tumor models of hepatocellular CSCs. Results: The ACNP have a similar size, a regular spherical shape and a smooth surface. The optimal ratio for adsorption was MET: ACNP=1:4. ACNP-MET could target and inhibit the proliferation of CD133+ population and decrease mammosphere formation and renewal of CD133+ population in vitro and in vivo. Conclusion: These results not only suggest that nanodrug delivery system increased the effects of MET, but also shed light on the mechanisms of the therapeutic effects of MET and ACNP-MET on hepatocellular cancers. ACNP, as a good nano-carrier, could strengthen the effect of MET by carrying drugs to the micro-environment of hepatocellular CSCs.

Study on tumour cell-derived hybrid exosomes as dasatinib nanocarriers for pancreatic cancer therapy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death. Therefore, we intend to explore novel strategies against PDAC. The exosomes-based biomimetic nanoparticle is an appealing candidate served as a drug carrier in cancer treatment, due to its inherit abilities. In the present study, we designed dasatinib-loaded hybrid exosomes by fusing human pancreatic cancer cells derived exosomes with dasatinib-loaded liposomes, followed by characterization for particle size (119.9 ± 6.10 nm) and zeta potential (-11.45 ± 2.24 mV). Major protein analysis from western blot techniques reveal the presence of exosome marker proteins CD9 and CD81. PEGylated hybrid exosomes showed pH-sensitive drug release in acidic condition, benefiting drug delivery to acidic cancer environment. Dasatinib-loaded hybrid exosomes exhibited significantly higher uptake rates and cytotoxicity to parent PDAC cells by two-sample t-test or by one-way ANOVA analysis of variance, as compared to free drug or liposomal formulations. The results from our computational analysis demonstrated that the drug-likeness, ADMET, and protein-ligand binding affinity of dasatinib are verified successfully. Cancer derived hybrid exosomes may serve as a potential therapeutic candidate for pancreatic cancer treatment.

An EGFR/HER2-targeted conjugate sensitizes gemcitabine-sensitive and resistant pancreatic cancer through different SMAD4-mediated mechanisms.

Chemoresistance limits its clinical implementation for pancreatic ductal adenocarcinoma (PDAC). We previously generated an EGFR/HER2 targeted conjugate, dual-targeting ligand-based lidamycin (DTLL), which shows a highly potent antitumor effect. To overcome chemoresistance in PDAC, we aim to study DTLL efficacy when combined with gemcitabine and explore its mechanisms of action. DTLL in combination with gemcitabine show a superior inhibitory effect on the growth of gemcitabine-resistant/sensitive tumors. DTLL sensitizes gemcitabine efficacy via distinct action mechanisms mediated by mothers against decapentaplegic homolog 4 (SMAD4). It not only prevents neoplastic proliferation via ATK/mTOR blockade and NF-κB impaired function in SMAD4-sufficient PDACs, but also restores SMAD4 bioactivity to trigger downstream NF-κB-regulated signaling in SMAD4-deficient tumors and to overcome chemoresistance. DTLL seems to act as a SMAD4 module that normalizes its function in PDAC, having a synergistic effect in combination with gemcitabine. Our findings provide insight into a rational SMAD4-directed precision therapy in PDAC.

Potential urinary biomarkers in young adults with short-term exposure to particulate matter and bioaerosols identified using an unbiased metabolomic approach.

Numerous epidemiological studies have shown a close relationship between outdoor air pollution and increased risks for cancer, infection, and cardiopulmonary diseases. However, very few studies have investigated the potential health effects of coexposure to airborne particulate matter (PM) and bioaerosols through the transmission of infectious agents, particularly under the current circumstances of the coronavirus disease 2019 pandemic. In this study, we aimed to identify urinary metabolite biomarkers that might serve as clinically predictive or diagnostic standards for relevant diseases in a real-time manner. We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites in 92 samples from young healthy individuals collected at three different time points after exposure to clean air, polluted ambient, or purified air, as well as two additional time points after air repollution or repurification. Subsequently, we compared the metabolomic profiles between the two time points using an integrated analysis, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathway and time-series analysis. We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure using GC/LC-MS and follow-up analyses, respectively. Our findings suggest that 16-dehydroprogesterone and 4-hydroxyphenylethanol in urine samples may serve as potential biomarkers to predict or diagnose PM- or bioaerosol-related diseases, respectively. The results indicated apparent differences between PM- and bioaerosol-associated DMs at five different time points and revealed dynamic alterations in the urinary metabolic profiles of young healthy humans with cyclic exposure to clean and polluted air environments. Our findings will help in investigating the detrimental health effects of short-term coexposure to airborne PM and bioaerosols in a real-time manner and improve clinically predictive or diagnostic strategies for preventing air pollution-related diseases.

Targeting therapy with mitosomal daunorubicin plus amlodipine has the potential to circumvent intrinsic resistant breast cancer.

Intrinsic resistance of cancers is a major cause of failure in chemotherapy. We proposed here a strategy to overcome intrinsic resistance by constructing cancer cell mitochondria-specifically targeting drug-loaded liposomes, namely, mitosomal daunorubicin plus amlodipine. Anticancer agent daunorubicin and apoptotic inducer amlodipine were loaded together into the mitosomes, and targeting molecule dequalinium was modified on the surface. Evaluations were performed on the breast cancer MCF-7 and resistant MCF-7/adr cells and in animals. Mitosomal daunorubicin plus amlodipine were about 97 nm, selectively accumulated in mitochondria, induced the swelling and disruption of mitochondria, dissipated the mitochondrial membrane potential, released a large amount of cytochrome C by translocation, cleaved Bid, and initiated a cascade of caspase 8 and 3 reactions. A robust anticancer effect was evidenced in vivo. Mitochondria-specifically targeting drug-loaded liposomes would provide a new strategy for treating resistant cancers.

Pharmacokinetics and tissue distribution of dual-targeting daunorubicin liposomes in mice.

BACKGROUND: To circumvent the problem of transporting anticancer drugs across the blood-brain barrier (BBB) to target brain tumors, we have previously developed dual-targeting daunorubicin liposomes modified with 4-aminophenyl-α-D-manno-pyranoside and transferrin molecules. The objective of the present study was to evaluate the pharmacokinetics and distribution of daunorubicin after intravenous administration of dual-targeting daunorubicin liposomes. METHODS: We evaluated pharmacological parameters in normal KunMing mice. Drug concentrations in plasma, heart, spleen, lung, kidney and brain were measured using HPLC-UV. RESULTS: The plasma drug concentration-time profile of the daunorubicin dual-targeting liposomes decreased more slowly than free daunorubicin in the initial phase and maintained higher drug levels in the terminal phase, resulting in longer blood exposure to daunorubicin liposomes compared with the free drug. Daunorubicin levels were lower in heart tissue and significantly higher in brain tissue after administration of the dual-targeting liposomes compared with the free drug. Daunorubicin was detected at varying levels in the liver, spleen, lung and kidney tissues. CONCLUSION: Our results indicate that dual-targeting daunorubicin liposomes improve the daunorubicin blood circulation time and show an enhanced drug transport potential across the BBB.

Role of argon plasma coagulation in treatment of esophageal varices.

With the development of endoscopic therapy, argon plasma coagulation (APC) has been widely used by endoscopists. It has many advantages, such as simple to operate, low cost, and minimal invasiveness. Because of its capability of lesion ablation and hemostasis, APC has several indications in the gastrointestinal tract. One of them is esophageal varices. The aim of this review is to summarize the research on APC in this field to provide a reference for clinical practice.

Effects of stealth liposomal daunorubicin plus tamoxifen on the breast cancer and cancer stem cells.

PURPOSE: The cancer stem cells play an important role in the invasion, metastasis and relapse of cancers as they are resistant to regular chemotherapy. In the present study, stealth liposomal daunorubicin plus tamoxifen was developed for eradicating breast cancer cells together with cancer stem cells. METHODS: Inhibitory effects were performed on the bulk human breast cancer cells (MCF-7), the sorted MCF-7 cancer stem-like cells (side population, SP), and the sorted MCF-7 cancer cells (NSP), respectively. Antitumor activity and TUNEL analysis were evaluated on the MCF-7 xenografts in nude mice. RESULTS: The encapsulation efficiencies of daunorubicin and tamoxifen were 95% and 90%, respectively. The mean particle size of the stealth liposomes was about 100 nm. Breast cancer stem cells were identified by the specific markers CD44+/CD24-, and isolated from bulk MCF-7 cells. When applying stealth liposomal daunorubicin plus tamoxifen, the inhibitory effects on both the breast cancer cells and the cancer stem cells were significantly increased in vitro, respectively. In the MCF-7 xenografts in mice, stealth liposomal daunorubicin plus tamoxifen showed the most favorable antitumor activity due to the passive targeting the tumor tissue and the synergistic effects in eliminating breast cancer cells and cancer stem cells. CONCLUSION: Stealth liposomal daunorubicin plus tamoxifen could have the potentials in eliminating both breast cancer cells and cancer stem cells.

Relationship between hemodynamic parameters and portal venous pressure in cirrhosis patients with portal hypertension.

Cirrhosis caused by viral and alcoholic hepatitis is an essential cause of portal hypertension (PHT). The incidence of PHT complication is directly proportional to portal venous pressure (PVP), and the clinical research of PVP and its hemodynamic indexes is of great significance for deciding the treatment strategy of PHT. Various techniques are currently being developed to decrease portal pressure but hemodynamic side effects may occur. In this article, the hemodynamic indexes of cirrhotic PHT patients were studied to explore the correlation between the index and PVP and to evaluate the clinical value of Doppler ultrasound in measuring PVP in patients with PHT. This was achieved by selecting 90 cirrhotic PHT patients who underwent transjugular intrahepatic portosystemic shunt in our hospital from June 2015 to September 2019. Fifty healthy people who had a physical examination in the hospital in the same period were selected as the control group. The liver hemodynamic parameters of two groups were measured by Doppler ultrasound, and the cirrhotic PHT patients were graded by the Child-Pugh grading method to evaluate the liver function and measure the PVP value. The results showed that both the central portal vein velocity (PVV) and splenic vein velocity (SVV) of the PHT group were lower than those of the control group. Also, the portal vein diameter (PVD), portal venous flow and splenic vein diameter (SVD) were higher than those of the control group (all Ps < 0.05). Among liver function graded PHT patients, the PVD, PVV, SVD and SVV were significantly different (all Ps < 0.05). Furthermore, the PVP of patients with liver function grades A, B and C was 38.9 ± 1.4, 40.6 ± 5.1 and 42.5 ± 4.8 cmH2O, respectively, with a significant difference. It can be concluded from this study that Doppler ultrasound can be used as a tool for clinical assessment of PHT in cirrhosis patients. Doppler ultrasound showed a good prospect in noninvasive detection of PHT in cirrhosis; however, this technique needs application on large sample population study to validate the results.

Four generations of EGFR TKIs associated with different pathogenic mutations in non-small cell lung carcinoma.

Non-small cell lung carcinoma (NSCLC) is a malignant tumour with poor prognosis and high mortality. Platinum-based dual-agent chemotherapy is the main therapeutic regimen for this disease. In recent years, because of the introduction of molecular targeted therapy, various targeted therapeutic agents against epidermal growth factor receptor (EGFR) have been rapidly developed, which has become a research hotspot for NSCLC treatment. Here, we review the latest studies describing the features and types of EGFR pathogenic mutations, currently established EGFR-tyrosine kinase inhibitors from the first to fourth generation, including their action mechanisms, acquired resistance, and clinical applications, and potential challenges and perspectives that current researchers should address.

A Novel Therapeutic siRNA Nanoparticle Designed for Dual-Targeting CD44 and Gli1 of Gastric Cancer Stem Cells.

PURPOSE: Gastric cancer stem cells (CSCs) are important for the initiation, growth, recurrence, and metastasis of gastric cancer, due to their chemo-resistance and indefinite proliferation. Herein, to eliminate gastric CSCs, we developed novel CSC-targeting glioma-associated oncogene homolog 1 (Gli1) small interfering RNA (siRNA) nanoparticles that are specifically guided by a di-stearoyl-phosphatidyl-ethanolamine- hyaluronic-acid (DSPE-HA) single-point conjugate, as an intrinsic ligand of the CD44 receptor. We refer to these as targeting Gli1 siRNA nanoparticles. METHODS: We used the reductive amination reaction method for attaching amine groups of DSPE to aldehydic group of hyaluronic acid (HA) at the reducing end, to synthesize the DSPE-HA single-point conjugate. Next, targeting Gli1 siRNA nanoparticles were prepared using the layer-by-layer assembly method. We characterized the stem cellular features of targeting Gli1 siRNA nanoparticles, including their targeting efficiency, self-renewal capacity, the migration and invasion capacity of gastric CSCs, and the penetration ability of 3D tumor spheroids. Next, we evaluated the therapeutic efficacy of the targeting Gli1 siRNA nanoparticles by using in vivo relapsed tumor models of gastric CSCs. RESULTS: Compared with the multipoint conjugates, DSPE-HA single-point conjugates on the surface of nanoparticles showed significantly higher binding affinities with CD44. The targeting Gli1 siRNA nanoparticles significantly decreased Gli1 protein expression, inhibited CSC tumor spheroid and colony formation, and suppressed cell migration and invasion. Furthermore, in vivo imaging demonstrated that targeting Gli1 siRNA nanoparticles accumulated in tumor tissues, showing significant antitumor recurrence efficacy in vivo. CONCLUSION: In summary, our targeting Gli1 siRNA nanoparticles significantly inhibited CSC malignancy features by specifically blocking Hedgehog (Hh) signaling both in vitro and in vivo, suggesting that this novel siRNA delivery system that specifically eliminates gastric CSCs provides a promising targeted therapeutic strategy for gastric cancer treatment.

Internal enhancement of DNA damage by a novel bispecific antibody-drug conjugate-like therapeutics via blockage of mTOR and PD-L1 signal pathways in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a refractory malignant tumor with poor prognosis, limited chemotherapeutic efficacy, and only about 5% of 5-year survival rate. We generated a dual-targeting ligand-based lidamycin (DTLL) to investigate its efficacy against pancreatic cancer after preparing its precursor, DTLP. DTLP was shown specifically binding to EGFR and HER2 on cell surface, followed by endocytosis into cytoplasm of pancreatic cancer cells. DTLL significantly promoted apoptosis and cell cycle arrest at G2/M stages and inhibited cell proliferation. Pancreatic tumors of either MIA-paca-2 cell line-derived (CDX) or patient-derived xenograft (PDX) mouse models were significantly regressed in response to DTLL. It suggested that DTLL might be a highly potent bispecific antibody-drug conjugate (ADC)-like agent for pancreatic cancer therapy. LDM is known to function as an antitumor cytotoxic agent by its induction of DNA damage in cancer cells, therefore, DTLL, as its derivative, also showed similar cytotoxicity. However, we found that DTLL might reverse the AKT/mTOR feedback activation induced by LDM at the first time. The results from both in vitro and in vivo experiments suggested that DTLL enhanced DNA damage via EGFR/HER2-dependent blockage of PI3K/AKT/mTOR and PD-L1 signaling pathways in cancer cells, leading to the inhibition of cell proliferation and immunosurveillance escape from pancreatic tumor. Our studies on DTLL functional characterization revealed its novel mechanisms on internal enhancement of DNA damage and implied that DTLL might provide a promising targeted therapeutic strategy for pancreatic cancer.

Matching from H(-) multicusp source to central region of a 100 MeV compact cyclotron for high current injection.

The way of matching the beam from an external ion source to the central region of the cyclotron CYCIAE-100 is presented in this article. The transverse acceptances of the central region were calculated, which provided the matching ellipse parameter requirements to the injection transport optics design. The optics of the injection line was simulated using TRANSOPTR, which allowed space charge effect calculation, and neutralization was taken into account.

Ion source and low energy injection line for a central region model cyclotron.

At CIAE, a 100 MeV H(-) cyclotron (CYCIAE-100) is under design and construction. A central region model (CRM) cyclotron was built for various experimental verifications for the CYCIAE-100 project and for research and development of high current injection to accelerate milliampere H(-) beam. The H(-) multicusp source built in 2003 has been improved recently to make the source operation more stable. A new injection line for axial low energy high current injection has been designed and constructed for the CRM cyclotron.

Folic Acid Functionalized γ-Cyclodextrin C60, A Novel Vehicle for Tumor-Targeted Drug Delivery.

Folic acid (FA)-γ cyclodextrin (γ CD)-C60 was synthesized in this study as a carrier for tumor-targeted drug delivery to enhance the anticancer effect of carboplatin (CBP). FA-γ CD and C60-CBP were prepared and C60-CBP was then entrapped into FA-γ CD through host-guest effect. FA-γ CD-C60 significantly increased the intracellular uptake and release of CBP, thereby providing higher cytotoxicity against the HeLa cells with high expression of folate receptor (FR). In vivo experiments revealed that FA-γ CD-C60-CBP had more significant anticancer effects than CBP alone, showing no obvious toxic effects on zebrafish at concentration as high as 500 µg/mL. These results suggest that FA-γ CD-C60 may provide an effective strategy for administration of antineoplastics, with great promise in future targeted therapy for cancers.