Ferric ions release from iron-binding protein: Interaction between acrylamide and human serum transferrin and the underlying mechanisms of their binding.

Acrylamide (ACR) is a surprisingly common chemical due to its widespread use in industry and various other applications. However, its toxicity is a matter of grave concern for public health. Even worse, ACR is frequently detected in numerous fried or baked carbohydrate-rich foods due to the Maillard browning reaction. Herein, this study intends to delineate the underlying molecular mechanisms of Fe ions released from iron-binding protein transferrin (TF) after acrylamide binding by combining multiple methods, including multiple complementary spectroscopic techniques (UV-Vis, fluorescence, and circular dichroism spectroscopy), isothermal titration calorimetry, ICP-MS measurements, and modeling simulations. Results indicated that free Fe was released from TF only under high-dose ACR exposure (>100 µM). Acrylamide binding induced the loosening and unfolding of the backbone and polypeptide chain and destroyed the secondary structure of TF, thereby leading to protein misfolding and denaturation of TF and forming a larger size of TF agglomerates. Of which, H-binding and van der Waals force are the primary driving force during the binding interaction between ACR and TF. Further modeling simulations illustrated that ACR prefers to bind to the hinge region connecting the C-lobe and N-lobe, after that it attaches to the Fe binding sites of this protein, which is the cause of free Fe release from TF. Moreover, ACR interacted with the critical fluorophore residues (Tyr, Trp, and Phe) in the binding pocket, which might explain such a phenomenon of fluorescence sensitization. The two binding sites (Site 2 and Site 3) located around the Fe (III) ions with low-energy conformations are more suitable for ACR binding. Collectively, our study demonstrated that the loss of iron in TF caused by acrylamide-induced structural and conformational changes of transferrin.

Increased serum catalytic iron may mediate tissue injury and death in patients with COVID-19.

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients-mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.

Expanding the Cross-Link Coverage of a Carboxyl-Group Specific Chemical Cross-Linking Strategy for Structural Proteomics Applications.

Carboxyl-group specific chemical cross-linking is gaining an increased interest as a structural mass spectrometry/structural proteomics technique that is complementary to the more commonly used amine-specific chemistry using succinimide esters. One of these protocols uses a combination of dihydrazide linkers and the coupling reagent DMTMM [4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium] chloride, which allows performing the reaction at neutral pH. The reaction yields two types of products, carboxyl-carboxyl cross-links that incorporate the dihydrazide linker and zero-length carboxyl-amine cross-links induced by DMTMM alone. Until now, it has not been systematically investigated how the balance between the two products is affected by experimental conditions. Here, we studied the role of the ratios of the two reagents (using pimelic dihydrazide and DMTMM) and demonstrate that the concentration of the two reagents can be systematically adjusted to favor one reaction product over the other. Using a set of five model proteins, we observed that the number of identified cross-linked peptides could be more than doubled by a combination of three different reaction conditions. We also applied this strategy to the bovine 20S proteasome and the Escherichia coli 70S ribosome, again demonstrating complementarity and increased cross-link coverage.

Rescue Potential of Supportive Embryo Culture Conditions on Bovine Embryos Derived from Metabolically Compromised Oocytes.

Elevated non-esterified fatty acid (NEFA), predominantly palmitic acid (PA), concentrations in blood and follicular fluid are a common feature in maternal metabolic disorders such as obesity. This has a direct negative impact on oocyte developmental competence and the resulting blastocyst quality. We use NEFA-exposure during bovine oocyte in vitro maturation (IVM) as a model to mimic oocyte maturation under maternal metabolic stress conditions. However, the impact of supportive embryo culture conditions on these metabolically compromised zygotes are not known yet. We investigated if the addition of anti-apoptotic, antioxidative and mitogenic factors (namely, Insulin-Transferrin-Selenium (ITS) or serum) to embryo culture media would rescue development and important embryo quality parameters (cell proliferation, apoptosis, cellular metabolism and gene expression patterns) of bovine embryos derived from high PA- or high NEFA-exposed oocytes when compared to controls (exposed to basal NEFA concentrations). ITS supplementation during in vitro culture of PA-exposed oocytes supported the development of lower quality embryos during earlier development. However, surviving blastocysts were of inferior quality. In contrast, addition of serum to the culture medium did not improve developmental competence of PA-exposed oocytes. Furthermore, surviving embryos displayed higher apoptotic cell indices and an aberrant cellular metabolism. We conclude that some supportive embryo culture supplements like ITS and serum may increase IVF success rates of metabolically compromised oocytes but this may increase the risk of reduced embryo quality and may thus have other long-term consequences.

Construction of synergistic therapy system with multiple therapeutic effects based on CuS@Tf nanodots.

In order to effectively avoid the side effects induced by multiple components and tedious synthesis process, a simple therapy system based on one material to simultaneously realize both photothermal therapy (PTT) and photodynamic therapy (PDT) under single laser irradiation will promote the overall phototherapeutic efficiency and make the PTT/PDT system easier to operate. Here, by using transferrin (Tf) as protein template, ultrasmall CuS@transferrin nanodots (CuS@Tf NDs) were successfully synthesized through a facile one-pot protein-based biomineralization method. The obtained CuS@Tf NDs exhibited not only excellent photothermal conversion ability (34.4%) but also high photoactivated formation of reactive oxygen species (ROS) upon 980 nm near-infrared (NIR) irradiation. By loading the drug doxorubicin (DOX) to CuS@Tf NDs, a synergistic therapy system with multiple therapeutic effects combined PTT, PDT, chemotherapy (CT) and tumor targeting properties could be perfectly implemented together by CuS@Tf-DOX NDs without any complicated post-modification process. Results from the in vitro cell experiments confirmed that these CuS@Tf-DOX NDs could produce excellent effect on cancer cells with 88.5% cell inhibition rate. In comparison with the complicated systems based on "multiple-components-in-one" strategy, this therapy system based on one single material but possess multifunctional purpose is easy to operate and more suitable for clinical applications.

Transferrin-functionalised microemulsion co-delivery of ß-elemene and celastrol for enhanced anti-lung cancer treatment and reduced systemic toxicity.

In this study, we developed an intravenously injectable, transferrin-functionalised microemulsion that simultaneously carries ß-elemene and celastrol (called Tf-EC-MEs) for enhanced anti-lung cancer treatment and reduced systemic toxicity. These dual-drug-loaded Tf-EC-MEs not only displayed synergistic antiproliferative effects on cultured cells in vitro, but also showed enhanced efficacy in vivo via active tumour targeting. In preparatory experiments, we found that ß-elemene was capable of being used as oil phase, which enhanced drug-loading efficiency and allowed the mass ratio of ß-elemene and celastrol to be optimised. In cellular studies, Tf-EC-MEs exhibited significantly improved A549 cellular uptake compared with ß-elemene+celastrol (conventional combination treatment) and EC-MEs (non-active targeted treatment), demonstrating remarkable synergistic antiproliferative effects and higher rates of cell apoptosis. In A549-bearing xenograft mouse tumour models, Tf-EC-MEs exhibited enhanced antitumour activity compared to all other treatments. More importantly, Tf-EC-MEs did not cause the obvious systemic toxicity commonly found with mono-celastrol treatment. Collectively, these findings suggest that Tf-EC-MEs are a promising strategy for the combination drug treatment of lung cancer.

Proteomic Sample Preparation through Extraction by Unspecific Adsorption on Silica Beads for ArgC-like Digestion.

Sample preparation for mass-spectrometry-based proteomic analyses usually requires intricate, multistep workflows that are often limited in capacity or suffer from sample loss. Here, we introduce a lean adsorption-based protocol (ABP) for the extraction of proteins from fresh cell lysates that enables us to modify and tag protein samples under harsh conditions, such as organic solvents, high salt concentrations, or low pH values. This offers high versatility while also reducing the required steps in the preparation process significantly. Protein identifications are slightly increased compared to traditional acetone precipitation followed by an in-solution digestion (AP/IS) or filter aided sample preparation (FASP) and proved complementary to both methods regarding proteome coverage. When combined with ArgC-like digestion, this approach delivered 5386 uniquely identified proteins, a substantial increase of 18.27% over tryptic digestion (4554), while decreasing spectra complexity due to a lower number of peptide to spectra matches per protein and the number of missed cleaved peptides. In addition, an increased number of identified membrane proteins and histones as well as improved fragmentation and intensity coverage were observed through comprehensive data analysis.

Evolutionary conservation of transferrin genomic organization and expression characterization in seven freshwater turtles.

Serum transferrin (tf), encoding an iron-binding glycoprotein, has been revealed to play important roles in iron transportation and immune response, and it also has been demonstrated to be valuable for phylogenetic analysis in vertebrates. However, the evolutionary conservation, expression profiles and positive selection of transferrin genes among freshwater turtle species remain largely unclear. Here, the genomic DNA and coding sequences of transferrin genes were cloned and characterized in seven freshwater turtles including Mauremys mutica, Mauremys sinensis, Cyclemys dentate, Mauremyssi reevesi, Heosemys grandis, Trachemys scripta and Chrysemys picta. The isolated coding sequences of turtles' tf genes were 2118 bp or 2121 bp, encoding 706 or 707 amino acids. The predicted Tf proteins of turtles share high identities with M. mutica Tf, up to 91%-98% and the M. mutica Tf has the highest identity (91%) in amino acid with the Chelomia mydas Tf, the moderate with other reptiles' Tfs (65%-59%), chicken (58%), and Human Tf (∼55%), and the lowest with zebrafish Tf (41%). Additionally, tf genes were consistently composed of 17 exons and 16 introns with the same splicing sites in introns in all the turtles examined. Moreover, 12 positive selected sites were detected in these turtles' Tf and mainly distributed on the surface of transferrin protein. Importantly, it was found that transferrin genes in all turtles examined were predominantly expressed in adult liver via real-time quantitative PCR. The molecular characterizations and expression profiles of transferrin would shed new insights into understanding the conversations and divergences of transferrin genes in turtles, even in vertebrates.

Ferric pyrophosphate citrate: interactions with transferrin.

There are several options available for intravenous application of iron supplements, but they all have a similar structure:-an iron core surrounded by a carbohydrate coating. These nanoparticles require processing by the reticuloendothelial system to release iron, which is subsequently picked up by the iron-binding protein transferrin and distributed throughout the body, with most of the iron supplied to the bone marrow. This process risks exposing cells and tissues to free iron, which is potentially toxic due to its high redox activity. A new parenteral iron formation, ferric pyrophosphate citrate (FPC), has a novel structure that differs from conventional intravenous iron formulations, consisting of an iron atom complexed to one pyrophosphate and two citrate anions. In this study, we show that FPC can directly transfer iron to apo-transferrin. Kinetic analyses reveal that FPC donates iron to apo-transferrin with fast binding kinetics. In addition, the crystal structure of transferrin bound to FPC shows that FPC can donate iron to both iron-binding sites found within the transferrin structure. Examination of the iron-binding sites demonstrates that the iron atoms in both sites are fully encapsulated, forming bonds with amino acid side chains in the protein as well as pyrophosphate and carbonate anions. Taken together, these data demonstrate that, unlike intravenous iron formulations, FPC can directly and rapidly donate iron to transferrin in a manner that does not expose cells and tissues to the damaging effects of free, redox-active iron.

Dual functionalized natural biomass carbon dots from lychee exocarp for cancer cell targetable near-infrared fluorescence imaging and photodynamic therapy.

Photodynamic therapy (PDT) is a non-invasive phototherapy that has gained significant attention for cancer therapy. However, image-guided PDT still remains a considerable challenge. Herein, we developed a targeted, near-infrared (NIR) fluorescence imaging nanoprobe for cancer cells by preparing natural biomass carbon dots (NBCDs) from lychee exocarp, and loading transferrin and a photosensitizer on the NBCD surfaces for image-guided PDT of cancer cells and mouse tumors. Because the surfaces of cancer cells exhibit more transferrin receptors, the proposed NIR fluorescent nanoprobe can better penetrate cancer cells for cancer cell targetable fluorescence imaging. Thus, the dual-function nanoprobe made from natural biomass can be used as a specific agent for NIR fluorescence imaging and PDT. More importantly, the functional nanoprobe prepared from natural biomass emits NIR fluorescence, shows very low biological toxicity, and can minimize side effects on normal cells. After directly injecting the nanoprobes into tumor tissues, the photosensitizers on the surface of the NBCDs can produce singlet oxygen (1O2) through photodynamic reactions when irradiated with 650 nm light to kill cancer cells, thus inhibiting tumor growth in PDT-treated mice. Therefore, the functional fluorescent nanoprobe made from natural biomass has been employed as a PDT agent, and holds great promise in image-guided tumor PDT.

The function of Eriocheir sinensis transferrin and iron in Spiroplasma eriocheiris infection.

Transferrin, a member of the iron binding superfamily protein, plays an extremely important role in the transport of iron in the biological process of cells. The result of preliminary proteomic study on E. sinensis hemocytes infected Spiroplasma eriocheiris showed the expression of transferrin (EsTF) and ferrin (EsFe) significantly changed. In addition, other reports have confirmed that transferrin, ferritin and iron are involved in the immune response of hosts. In order to validate the immune function of EsTF, the whole length of EsTF was successfully amplified by the gene cloning and RACE technique. The results showed that the full-length cDNA of the EsTF gene was 2748 bp, including a 2193 bp open reading frame which encodes 730 amino acids. The result of bioinformatics analysis showed EsTF contains two highly conserved TR_FER domains. Evolutionary analysis showed that EsTF has a close genetic relationship with other TFs of invertebrates. In addition, EsTF mRNA was highly transcripted in nerve and intestine tissues, followed by hemocytes. The expression of EsTF, EsFe1 and EsFe2 increased after exogenous supplemental of iron under the concentration of 100 nmol/L in water. After exogenous supplement of iron and injection with S. eriocheiris, these three gene transcription of mRNA levels were higher than that of PBS group, while lower than the S. eriocheiris group and the iron group. Besides, the copy number of S. eriocheiris in the experimental group was significantly reduced, and the death rate decreased. As can be seen, iron made transferrin and ferritin return to normal levels during the infection of S. eriocheiris and help the host maintain normal immunity levels to resist S. eriocheiris. These results further demonstrated that EsTF, EsFe1, EsFe2 and iron play a role in the immune defense mechanism of the crabs to resist S. eriocheiris infection.

Transferrin modified ruthenium nanoparticles with good biocompatibility for photothermal tumor therapy.

In the past two decades, there were various kinds of photothermal agents being synthesised and investigated for their photothermal effect in antitumor applications. However, it is barely reported that the photothermal effect of Ruthenium (Ru) nanoparticles was researched in depth. In this work, we introduced Ru nanoparticles which possess excellent biocompatibility and metabolize easily to the photothermal therapy field. In addition, to improve the cells capacity of absorbing Ru nanoparticles, these Ru nanoparticles were modified by transferrin (Tf-RuNPs). Subsequently, as is expected, the RuNPs exhibit a remarkably integrated and high-quality photothermal property. On the other hand, it is significantly that Tf modification could also strengthen the cells absorptive ability to uptake Ru nanoparticles through endocytosis., Furthermore, both the in vitro cell ablation and in vivo tumor treatment verified that the Tf-RuNPs became ideal photothermal agents for photothermal tumor ablation therapy owing to their low toxicity and high cell destruction capability.

Iodine-131-labeled, transferrin-capped polypyrrole nanoparticles for tumor-targeted synergistic photothermal-radioisotope therapy.

Combining different therapeutic functions within single tumor-targeted nanoscale delivery systems is promising to overcome the limitations of conventional cancer therapies. Herein, transferrin that recognizes transferrin receptors up-regulated on tumor cells is pre-labeled with iodine-131 (131I) and then utilized as the stabilizer in the fabrication of polypyrrole (PPy) nanoparticles. The obtained transferrin-capped PPy@Tf-131I nanoparticles could be used for tumor-targeted radioisotope therapy (RIT) and photothermal therapy (PTT), by employing beta-emission from 131I and the intrinsic high near-infrared (NIR) absorbance of PPy, respectively. Owing to the transferrin-mediated tumor targeting, PPy@Tf-131I nanoparticles exhibit obviously enhanced in vitro cancer cell binding and in vivo tumor uptake compared to its non-targeting counterpart. The combined RIT and PTT based on PPy@Tf-131I nanoparticles is then conducted, achieving a remarkable synergistic therapeutic effect. This work thus demonstrates a rather simple one-step approach to fabricate tumor-targeting nanoparticles based on protein-capped conjugated polymers, promising for combination cancer therapy with great efficacy and high safety.

Co-delivery of doxorubicin and pH-sensitive curcumin prodrug by transferrin-targeted nanoparticles for breast cancer treatment.

The natural product curcumin and the chemotherapeutic agent doxorubicin have been used in the treatment of many cancers, including breast cancer. However, fast clearance and unspecific distribution in the body after intravenous injection are still challenges to be overcome by an ideal nano-sized drug delivery system in cancer treatment. In this study we design transferrin (Tf) decorated nanoparticles (NPs) to co-deliver CUR and DOX for breast cancer treatment. A pH-sensitive prodrug, transferrin-poly(ethylene glycol)-curcumin (Tf-PEG-CUR), was synthesized and used for the self­assembling of NPs (Tf-PEG-CUR NPs). DOX is incorporated into the Tf-PEG-CUR NPs to obtain Tf-PEG-CUR/DOX NPs. In vitro cytotoxicity studies and in vivo antitumor activity were carried out using MCF-7 cells and mice bearing MCF-7 cells, respectively. Tf-PEG-CUR/DOX NPs has a particle size of 89 nm and a zeta potential of -15.6 mV. This system displayed remarkably higher efficiency than other systems both in vitro and in vivo. DOX and CUR were successfully loaded into nanocarriers. The in vitro cell viability assays revealed the combination of Tf-PEG-CUR and DOX NPs exhibited higher cytotoxicity in vitro in MCF-7 cells compared with Tf-PEG-CUR NPs alone. Using the breast cancer xenograft mouse model, we demonstrate that this co-encapsulation approach resulted in an efficient tumor-targeted drug delivery, decreased cytotoxic effects and exhibited stronger antitumor effect.

The immune properties of Manduca sexta transferrin.

Transferrins are secreted proteins that bind iron. The well-studied transferrins are mammalian serum transferrin, which is involved in iron transport, and mammalian lactoferrin, which functions as an immune protein. Lactoferrin and lactoferrin-derived peptides have bactericidal activity, and the iron-free form of lactoferrin has bacteriostatic activity due to its ability to sequester iron. Insect transferrin is similar in sequence to both serum transferrin and lactoferrin, and its functions are not well-characterized; however, many studies of insect transferrin indicate that it has some type of immune function. The goal of this study was to determine the specific immune functions of transferrin from Manduca sexta (tobacco hornworm). We verified that transferrin expression is upregulated in response to infection in M. sexta larvae and determined that the concentration of transferrin in hemolymph increases from 2 µM to 10 µM following an immune challenge. It is also present in molting fluid and prepupal midgut fluid, two extracellular fluids with immune capabilities. No immune-induced proteolytic cleavage of transferrin in hemolymph was observed; therefore, M. sexta transferrin does not appear to be a source of antimicrobial peptides. Unlike iron-saturated lactoferrin, iron-saturated transferrin had no detectable antibacterial activity. In contrast, 1 µM iron-free transferrin inhibited bacterial growth, and this inhibition was blocked by supplementing the culture medium with 1 µM iron. Our results suggest that M. sexta transferrin does not have bactericidal activity, but that it does have a bacteriostatic function that depends on its iron sequestering ability. This study supports the hypothesis that insect transferrin participates in an iron withholding strategy to protect insects from infectious bacteria.

Theranostic Polyaminocarboxylate-Cyanine-Transferrin Conjugate for Anticancer Therapy and Near-Infrared Optical Imaging.

Iron chelation therapy has been recognized as a promising antitumor therapeutic strategy. Herein we report a novel theranostic agent for targeted iron chelation therapy and near-infrared (NIR) optical imaging of cancers. The theranostic agent was prepared by incorporation of a polyaminocarboxylate-based cytotoxic chelating agent (N-NE3TA; 7-[2-[(carboxymethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) and a NIR fluorescent cyanine dye (Cy5.5) onto a tumor-targeting transferrin (Tf). The N-NE3TA-Tf conjugate (without Cy5.5) was characterized and evaluated for antiproliferative activity in HeLa, HT29, and PC3 cancer cells, which have elevated expression levels of the transferrin receptor (TfR). The N-NE3TA-Tf conjugate displayed significant inhibitory activity against all three cancer cell lines. The NIR dye Cy5.5 was then incorporated into N-NE3TA-Tf, and the resulting cytotoxic and fluorescent transferrin conjugate N-NE3TA-Tf-Cy5.5 was shown by microscopy to enter TfR-overexpressing cancer cells. This theranostic conjugate has potential application for dual use in targeted iron chelation cancer therapy and NIR fluorescence imaging.

Green and facile synthesis of a theranostic nanoprobe with intrinsic biosafety and targeting abilities.

Traditional targeting nanoprobes suffer from the risks of partial loss of targeting activity and nanoparticle aggregation induced by post-synthetic modifications, ambiguous toxicity, tedious synthesis procedures and environmentally hazardous processes. Herein, we report a green and facile strategy to fabricate transferrin-indocyanine green nanoparticles as a smart theranostic agent with intrinsic biosafety and active targeting abilities for near-infrared fluorescent imaging and photothermal therapy of tumors. Simple mixing of transferrin and indocyanine green enables their self-assembly in aqueous solution to form nanoparticles with excellent water solubility, colloidal stability, favorable biocompatibility and impressive active targeting theranostic effects in vitro and in vivo. The transferrin-indocyanine green nanoparticles show great potential in theranostic applications of tumors in clinical therapy.

Self-assembled IR780-loaded transferrin nanoparticles as an imaging, targeting and PDT/PTT agent for cancer therapy.

Combination of photothermal and photodynamic therapy (PTT/PDT) offer unique advantages over PDT alone. However, to achieve synergetic PDT/PTT effect, one generally needs two lasers with different wavelengths. Near-infrared dye IR-780 could be used as photosensitizer both for PTT and PDT, but its lipophilicity limits its practical use and in vivo efficiency. Herein, a simple multifunctional IR780-loaded nanoplatform based on transferrin was developed for targeted imaging and phototherapy of cancer compatible with a single-NIR-laser irradiation. The self-assembled transferrin-IR780 nanoparticles (Tf-IR780 NPs) exhibited narrow size distribution, good photo-stability, and encouraging photothermal performance with enhanced generation of ROS under laser irradiation. Following intravenous injection, Tf-IR780 NPs had a high tumor-to-background ratio in CT26 tumor-bearing mice. Treatment with Tf-IR780 NPs resulted in significant tumor suppression. Overall, the Tf-IR780 NPs show notable targeting and theranostic potential in cancer therapy.

In vitro and in vivo brain-targeting chemo-photothermal therapy using graphene oxide conjugated with transferrin for Gliomas.

Current therapies for treating malignant glioma exhibit low therapeutic efficiency because of strong systemic side effects and poor transport across the blood brain barrier (BBB). Herein, we combined targeted chemo-photothermal glioma therapy with a novel multifunctional drug delivery system to overcome these issues. Drug carrier transferrin-conjugated PEGylated nanoscale graphene oxide (TPG) was successfully synthesized and characterized. When loaded on the proposed TPG-based drug delivery (TPGD) system, the anticancer drug doxorubicin could pass through the BBB and improve drug accumulation both in vitro and in vivo. TPGD was found to perform dual functions in chemotherapy and photothermal therapy. Targeted TPGD combination therapy showed higher rates of glioma cell death and prolonged survival of glioma-bearing rats compared with single doxorubicin or PGD therapy. In conclusion, we developed a potential nanoscale drug delivery system for combined therapy of glioma that can effectively decrease side effects and improve therapeutic effects.

Secondary haemochromatosis in a haemodialysis patient.

A 39-year-old woman with end-stage renal disease, which was maintained on haemodialysis, developed secondary haemochromatosis after receiving blood transfusions and intravenous iron supplementation without sufficient serum ferritin concentration monitoring. The patient received intravenous deferoxamine three times a week, combined with high-dose recombinant human erythropoietin therapy and haemodialysis. After three months, improvements in biochemical indicators and iron overload were noted.