Targeting Carrier Research Articles

RGDS covalently surfaced nanodiamond as a tumor targeting carrier of VEGF-siRNA: synthesis, characterization and bioassay.

A nonviral tumor targeting vector for siRNA transfer is of importance. Here, a novel delivery system consisting of a covalent conjugate of NDCO-RGDS and VEGF-siRNA, NDCO-RGDS/VEGF-siRNA, was presented. In vitro, NDCO-RGDS/VEGF-siRNA released and transferred VEGF-siRNA in a long-acting manner. Compared to the control, NDCO-RGDS/VEGF-siRNA decreased the expression of VEGF mRNA and protein in HeLa cells by 88.41 ± 3.49% and 83.94 ± 2.00%, respectively. In vivo, NDCO-RGDS/VEGF-siRNA exhibited gene silencing and slowed tumor growth. FT-MS spectrum analysis revealed that NDCO-RGDS/VEGF-siRNA mainly distributed in tumor tissue of the treated S180 mice. Therefore NDCO-RGDS could be considered a promising nonviral tumor-targeting vector for siRNA transfer in tumor therapy.

Designing casein-coated iron oxide nanostructures (CCIONPs) as superparamagnetic core-shell carriers for magnetic drug targeting.

Magnetic drug targeting is a drug delivery system applicable to cancer treatment. Coated magnetic particles, called carriers, are very useful for delivering chemotherapeutic drugs. In the present research, casein-coated iron oxide nanocarriers (CCIONPs) of core shell nanostructure have been described as being applicable to magnetic drug targeting. The structure, morphology, and composition of prepared magnetic nanoparticles were determined by analytical techniques like Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Electron diffraction (ED), X-ray diffraction (XRD), Zeta potential, Dynamic light scattering (DLS), Mossbauer and Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), Vibrating sample magnetometery (VSM)) and in vitro cytotoxicity analysis. Magnetization studies of CCIONPs conducted at room temperature using a vibrating sample magnetometer suggested their superparamagnetic nature as having a saturation magnetization (Ms) of 64 emu g−1 at an applied magnetic field of 5 kOe. The size of the magnetic polymeric nanoparticles was found to lie in the range of 73.9 ±0.36 nm, and the particles exhibited superparamagnetic behavior. The prepared particles could be used as a drug carrier for controlled and targeted drug delivery.

Abstract 4471: AD-O64.4 - a novel bioconjugate for tumor-targeted drug delivery

Abstract Although standard chemotherapy is still one of the most effective treatment for many types of cancer - often causes side effects. Chemotherapeutic agents primarily damage cancer cells with a rapidly dividing and growing profile, thereby also destroy healthy cells with such characteristics, which leads to side effects. Scientists are continually working to identify new, safer drugs, methods of administering chemotherapy, and combinations of existing treatments that have fewer side effects. In recent years, drug delivery systems (DDS) based on a concept of conjugation anticancer agents to carrier protein have been developed, achieving a better clinical response and tolerability. Protein-drug conjugates represent a whole new concept for cancer treatment which, although highly effective, cause much fewer sides effects than traditional chemotherapy. The present work is aimed to create a new conjugate molecule which essentially demonstrates greater effect than the summarized effects of its components due to specific targeting to cancer cells. We generated AD-O64.4 complex molecule, consisting of fusion protein INF- γ - TRAIL/Apo2L conjugated with the anti-mitotic agent SN-38 via the thioether linker. Carrier protein is a fusion molecule which is composed of soluble fragment of TRAIL (acting as a targeting carrier and effector) fused with artificial dimer of IFN-γ (acting as effector). SN-38, a topoisomerase I inhibitor with low nanomolar potency, the active metabolite of irinotecan, cannot be given directly to patients because of its toxicity and poor solubility. Linking SN-38 to the carrier fusion protein results in selective drug delivery to tumors which consequently leads to increased amount of the drug reaching the tumors and minimized damage of healthy cells. Analysis of the conjugate was performed by LC-MS and resulted in determination of drug-protein ratio. Agregation studies of the molecule complex were conducted by DLS and fluorescent protein aggregation assay. Cytotoxicity was evaluated with MTT assay and efficacy was performed on female SCID mice xenograft model bearing Human Uterine Sarcoma (MES-SA/Dx5). Our results show an effective process of conjugation of anticancer compound SN-38 to the carrier protein which leads to formation of an active complex with enhanced efficacy. AD-O64.4 exhibited cytotoxic effect on various cancer cell lines, (IC50 about 10 ng/ml), but showed no toxic effect on normal cells. This conjugate was also highly cytotoxic against primary cancer cells. AD-O64.4 was highly active (up to 75% tumor remission) against subcutaneous multiple drug resistant, MES-SA/Dx5, tumor xenografts in severe combined immunodeficient mice with better activity compared to the carrier protein alone, as well as to combination of the carrier protein with free-drug. Overall, these results represent a novel and a valuable system for drug delivery to the tumor and its microenvironment. Citation Format: Wojciech Strozek, Anna Pieczykolan, Bartlomiej Zerek, Michal Szymanik, Albert Jaworski, Marlena Galazka, Katarzyna Bukato, Piotr Rozga, Sebastian Pawlak, Katarzyna Poleszak, Malgorzata Teska-Kaminska, Jerzy Pieczykolan. AD-O64.4 - a novel bioconjugate for tumor-targeted drug delivery. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4471. doi:10.1158/1538-7445.AM2014-4471

Synthesis and evaluation of glyco-coated liposomes as drug carriers for active targeting in drug delivery systems

Novel sugar-conjugated cholesterols, β-Gal-, α-Man-, β-Man-, α-Fuc-, and β-Man-6P-S-β-Ala-Chol, were synthesized and incorporated into liposomes. In vitro experiments using the glyco-coated liposomes showed that the glyco-coated liposomes are efficiently taken up by cells expressing carbohydrate-binding receptors selectively. Glyco-coated liposomes are promising candidates for drug delivery vehicles.

Targetable micelleplex hydrogel for long-term, effective, and systemic siRNA delivery

We developed a targetable micelleplex hydrogel as a new efficient systemic siRNA delivery material that functions as a targetable gene carrier, and a hydrogel capable of controlled release to overcome drawbacks of multiple administrations of systemic siRNA carriers due to decreased fluctuation of them in the serum. The micelleplexes, complexes between polymeric micelles and siRNAs could turn into gel after subcutaneous injection and be slowly released from the gel. The released micelleplexes selectively accumulated in the tumor and showed anti-tumor effect due to gene silencing for an extended period of time with only one injection in anywhere in vivo model. Moreover, the duration of therapy can be controlled by adjusting the amount and properties of the hydrogel. Therefore, this micelleplex hydrogel is expected to be a new effective siRNA delivery material for systemic long-term gene silencing.

Study on intralymphatic-targeted hyaluronic acid-modified nanoliposome: Influence of formulation factors on the lymphatic targeting

In this study, hyaluronic acid-modified docetaxel-loaded liposomes were prepared to evaluate the lymphatic targeting after subcutaneous administration, and formulation factors affecting the lymphatic targeting were examined, including free hyaluronic acid, molecular weight, hyaluronic acid-density and particle diameter. The high molecular weight hyaluronic acid-modified docetaxel-loaded liposomes (HA-LPs) and low molecular weight hyaluronic acid-modified docetaxel-loaded liposomes (LMWHA-LPs) were prepared via electrostatic attraction. The physicochemical properties and in vitro drug release were evaluated. The lymphatic drainage and the lymph node uptake were investigated by pharmacokinetics and distribution recovery of docetaxel in lymph nodes, injection site and plasma. The lymphatic targeting ability of optimized Cy7-loaded LMWHA-LPs (LMWHA-LPs/Cy7) was evaluated by near-infrared fluorescence imaging technique. The result showed that HA-LPs and LMWHA-LPs with suitable and stable physicochemical properties could be used for in vivo lymphatic targeting studies. Hyaluronic acid-modified liposome significantly increased the docetaxel recovery in lymph nodes, and displayed higher AUC(0-24h) and longer retention time compared to unmodified liposomes in vivo. In contrast, the presence of free hyaluronic acid hindered the lymphatic drainage and increased the plasma-drug concentration. Importantly, LMWHA-modification improved lymphatic drainage and lymph node uptake of liposomes compared with HA-modification. And Lymph node uptake of LMWHA-LPs depended mainly on LMWHA-density instead of particle size. The results of in vivo imaging showed that LMWHA-LPs/Cy7 significantly located in the lymphatic system. And both DTX-loaded and Cy7-loaded LMWHA-LPs had similar and stable lymphatic target level. Our investigation showed that LMWHA-LPs were a highly promising lymphatic targeting carrier for chemotherapy drugs and diagnostic fluorescence agents.

Investigation of cyanine dyes for in vivo optical imaging of altered mitochondrial membrane potential in tumors.

Mitochondrial membrane potential (Δψm) alteration is an important target for cancer diagnosis. In this study, we designed a series of near-infrared fluorescent cationic cyanine dyes with varying alkyl chain lengths (IC7-1 derivatives) to provide diverse lipophilicities and serum albumin-binding rates, and we evaluated the usefulness of these derivatives for in vivo Δψm imaging. IC7-1 derivatives with side chains from methyl to hexyl (IC7-1-Me to IC7-1-He) were synthesized, and their optical properties were measured. Cellular uptake and intracellular distribution were investigated with depolarized HeLa cells from carbonyl cyanine m-chlorophenylhydrazone (CCCP) treatment using a spectrofluorometer and a fluorescence microscope. Serum albumin-binding rates were evaluated using albumin-binding inhibitors. In vivo optical imaging was performed with HeLa cell xenograft mice following intravenous administration of IC7-1 derivatives with or without warfarin and CCCP as in vivo blocking agents. IC7-1 derivatives showing maximum excitation and emission wavelengths at 823 nm and ∼845 nm, respectively, were synthesized. IC7-1-Me to -Bu showed fluorescence in mitochondria that decreased with CCCP treatment in a concentration-dependent manner, which showed that IC7-1-Me to -Bu successfully indicated Δψm. Tumors were clearly visualized after IC7-1-Bu administration. Treatment with warfarin or CCCP significantly decreased IC7-1-Bu fluorescence in the tumor region. In summary, IC7-1-Bu exhibited fluorescence localized to mitochondria dependent on Δψm, which enabled clear in vivo tumor imaging via serum albumin as a drug carrier for effective tumor targeting. Our data suggest that IC7-1-Bu is a promising NIR probe for in vivo imaging of the altered Δψm of tumor cells.

Glycol Chitosan‐Based Nanogel as a Potential Targetable Carrier for siRNA

Macromol. Biosci. 2013, 13, 1369–1378 DOI: 10.1002/mabi.201300123 We regret that Figure 7 of this manuscript was published as a duplicate of Figure 6. The correct Figure 7 is provided here:

Polymer Micro‐ and Nanocapsules as Biological Carriers with Multifunctional Properties

The design and development of multifunctional polymer capsules with controlled chemical composition and physical properties has been the focus of academic and industrial research in recent years. Especially in the biomedical field, the formulation of novel polymer-based encapsulation systems for the early-stage disease diagnostic and effective delivery of bioactive agents represent one of the most rapidly advancing areas of science. The stimuli-responsive release of cargo molecules from the carrier gains remarkable attention for in vitro and in vivo delivery of contrast agents, genes, and pharmaceutics. In this Review, the current status and the challenges of different polymer-based micro- and nanocapsule formulations are considered, emphasizing on their potential biological application as carriers for specific drug targeting and controlled release upon applying of external stimulus.

Galactosylated polymeric carriers for liver targeting of sorafenib

In this paper, we describe the preparation of liver-targeted polymeric micelles potentially able to carry sorafenib to hepatocytes for treatment of hepatocarcinoma (HCC), exploiting the presence of carbohydrate receptors, ASGPR. These micelles were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-d,l-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, leading to PHEA-EDA-PLA-GAL copolymer. Liver-targeted sorafenib-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometer size and slightly positive zeta potential. Biodistribution studies on mice demonstrated, after oral administration of sorafenib loaded PHEA-EDA-PLA-GAL micelles, the preferential sorafenib accumulation into the liver. This finding raises hope in terms of future drug delivery strategy of sorafenib-loaded micelles targeted to the liver for the HCC treatment.

Peptide conjugated polymeric nanoparticles as a carrier for targeted delivery of docetaxel

The aim of this research work was to develop Bombesin peptide (BBN) conjugated, docetaxel loaded nanocarrier for the treatment of breast cancer. Docetaxel loaded nanoparticles (DNP) were prepared by solvent evaporation method using sodium cholate as surfactant. BBN was conjugated to DNP surface through covalent bonding. Both DNP and BBN conjugated DNP (BDNP) were characterized by various techniques such as dynamic light scattering, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis. The particle diameter and zeta potential of BDNP were 136±3.95nm and −10.8±2.7mV, respectively. The change in surface charge and FTIR studies confirmed the formation of amide linkage between BBN and DNP. AFM analysis showed that nanoparticles were spherical in shapes. In nanoparticles, docetaxel was present in its amorphous form as confirmed by DSC and PXRD analysis and was stable during the thermal studies. The formulations showed the sustained release of DTX over the period of 120h. During cellular toxicity assay in gastrin releasing peptide receptor positive breast cancer cells (MDA-MB-231), BDNP were found to be 12 times more toxic than pure DTX and Taxotere. The IC50 value for DTX, Taxotere, DNP and BDNP was >375, >375, 142.23 and 35.53ng/ml, respectively. The above studies showed that Bombesin conjugated nanocarrier system could be a promising carrier for active targeting of anticancer drugs in GRP receptor over expressing cancer cells.

Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague

Yersinia pestis F1 antigen-loaded poly(DL-lactide-co-glycolide)/polyethylene glycol (PEG) (PLGA/PEG) microspheres were produced using a water-in-oil-in-water emulsion/solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. The Y. pestis F1 antigen-loaded microspheres (mean particle size 3.8 μm) exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (38.1%), and presented a controlled in vitro release profile with a low initial burst (18.5%), then continued to release Y. pestis F1 antigen over 70 days. The distribution (%) of Y. pestis F1 on the microspheres surface, outer layer, and core was 3.1%, 28.9%, and 60.7%, respectively. A steady release rate was noticed to be 0.55 μg Y. pestis F1 antigen/mg microspheres/day of Y. pestis F1 antigen release maintained for 42 days. The cumulative release amount at the 1st, 28th, and 42nd days was 8.2, 26.7, and 31.0 μg Y. pestis F1 antigen/mg microspheres, respectively. The 100 times median lethal dose 50% (LD50) of Y. pestis Yokohama-R strain by intraperitoneal injection challenge in mice test, in which mice received one dose of 40 μg F1 antigen content of PLGA/PEG microspheres, F1 antigen in Al(OH)3, and in comparison with F1 antigen in Al(OH)3 vaccine in two doses, was evaluated after given by subcutaneous immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1 antigen-loaded PLGA/PEG microspheres, and two doses of F1 antigen in Al(OH)3 vaccine (100%). In vivo vaccination studies also demonstrated that F1 vaccines microspheres had a protective ability; its steady-state IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764±3,124) to 7 weeks (126,468±19,176) after vaccination. These findings strongly suggest that F1-antigen loaded microspheres vaccine offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.

Endothelial targeting of nanocarriers loaded with antioxidant enzymes for protection against vascular oxidative stress and inflammation

Endothelial-targeted delivery of antioxidant enzymes, catalase and superoxide dismutase (SOD), is a promising strategy for protecting organs and tissues from inflammation and oxidative stress. Here we describe Protective Antioxidant Carriers for Endothelial Targeting (PACkET), the first carriers capable of targeted endothelial delivery of both catalase and SOD. PACkET formed through controlled precipitation loaded ∼30% enzyme and protected it from proteolytic degradation, whereas attachment of PECAM monoclonal antibodies to surface of the enzyme-loaded carriers, achieved without adversely affecting their stability and functionality, provided targeting. Isotope tracing and microscopy showed that PACkET exhibited specific endothelial binding and internalization in vitro. Endothelial targeting of PACkET was validated in vivo by specific (vs IgG-control) accumulation in the pulmonary vasculature after intravenous injection achieving 33% of injected dose at 30 min. Catalase loaded PACkET protects endothelial cells from killing by H2O2 and alleviated the pulmonary edema and leukocyte infiltration in mouse model of endotoxin-induced lung injury, whereas SOD-loaded PACkET mitigated cytokine-induced endothelial pro-inflammatory activation and endotoxin-induced lung inflammation. These studies indicate that PACkET offers a modular approach for vascular targeting of therapeutic enzymes.

Lactoferrin-appended solid lipid nanoparticles of paclitaxel for effective management of bronchogenic carcinoma

Lung cancer is a dreadful disease which claims to be more life threatening as compared to total sum up of colon, prostate and breast cancers. Thus, there is an urgent need to develop an effective delivery approach for its management. Paclitaxel (PTX) is one of the well-known choice as antineoplasitic agent used for the treatment of different types of human cancers such as non-small-cell lung, head and neck cancers, leukemia, breast, ovarian and melanoma. Lactoferrin (Lf), a “multifunctional protein” is crucial for natural immunity which is secreted by exocrine glands. Lf receptors are expressed on the apical surface on bronchial epithelial cells. These over-expressed LF receptors can be utilized for the transportation of Lf-conjugated drug or nanocarrier devices. The present study was aimed to develop PTX-loaded Lf-coupled solid lipid nanoparticles (SLNs) for the treatment of lung cancer. PTX-loaded SLNs were prepared, characterized and then coupled with Lf using carbodiimide chemistry. The formulations were characterized by transmission electron microscopy, particle size, polydispersity index and zeta potential, whereas Lf conjugation was confirmed by FT-IR and 1H NMR and efficiency of prepared system was evaluated by in vitro, ex vivo and in vivo evaluations. The ex vivo cytotoxicity studies on human bronchial epithelial cell lines, BEAS-2B, revealed superior anticancer activity of Lf-coupled SLNs than plain SLNs and free PTX. In vivo biodistribution studies showed higher concentrations of PTX accumulated in lungs via Lf-coupled SLNs than plain SLNs and free PTX. These studies suggested that Lf-coupled PTX-loaded SLNs could be used as potential targeting carrier for delivering anticancer drug to the lungs with the minimal side effects.

Development of etoposide-loaded bovine serum albumin nanosuspensions for parenteral delivery

Nanosuspensions emerge as a promising strategy for delivery of poorly water-soluble drugs. Albumin is a versatile protein carrier for drug delivery and targeting. The purpose of this study was to develop a formulation of etoposide-loaded bovine serum albumin (BSA) nanosuspensions, to study in vitro characterization, and to estimate the in vivo safety and tissue distribution of etoposide-loaded BSA nanosuspensions for parenteral delivery. Etoposide-loaded BSA nanosuspensions were prepared by high-pressure homogenization-solvent precipitation method. The particle size, zeta potential, drug entrapment efficiency, and drug loading of the lyophilized formulation were 182.3 nm, −22.18 mV, 86.44%, and 8.49% respectively. In vitro release files of the formulation presented sustained release properties. Preliminary safety study was conducted to evaluate the delivery system, and results indicated that myelosuppression effect of the etoposide-loaded BSA nanosuspensions group was significantly lower than the Injection® group. Furthermore, results of tissue distribution studies showed that the concentration and AUC of etoposide were increased significantly in lung, liver, spleen while reduced in heart, kidney compared with the etoposide injection® group after i.v. administration of etoposide-loaded BSA nanosuspensions. The formulation played a role in targeting delivery to lung, reduce toxicity, and side effects of etoposide. In conclusion, etoposide-loaded BSA nanosuspensions were promising for parenteral delivery of etoposide.

Renal protein reactivity and stability of antibiotic amphenicols: structure and affinity.

In the present work, the molecular recognition of the oldest active amphenicols by the most popular renal carrier, lysozyme, was deciphered by using fluorescence, circular dichroism (CD) and molecular modeling at the molecular scale. Steady state fluorescence data showed that the recognition of amphenicol by lysozyme yields a static type of fluorescence quenching. This corroborates time-resolved fluorescence results that lysozyme-amphenicol adduct formation has a moderate affinity of 10(4) M(-1), and the driving forces were found to be chiefly hydrogen bonds, hydrophobic interactions and π stacking. Far-UV CD spectra confirmed that the spatial structure of lysozyme was slightly changed with a distinct reduction of α-helices in the presence of amphenicol, suggesting partial destabilization of the protein. Furthermore, via the extrinsic 8-anilino-1-naphthalenesulfonic acid fluorescence spectral properties and molecular modeling, one could see that the amphenicol binding site was situated at the deep crevice on the protein surface, and the ligand was also near to several crucial amino acid residues, such as Trp-62, Trp-63 and Arg-73. Simultaneously, contrastive studies of protein-amphenicols revealed clearly that some substituting groups, e.g. nitryl in the molecular structure of ligands, may be vitally important for the recognition activity of amphenicols with lysozyme. Due to the connection of amphenicols with fatal detrimental effects and because lysozyme has been applied as a drug carrier for proximal tubular targeting, the discussion herein is necessary for rational antibiotic use, development of safe antibiotics and particularly a better appraisal of the risks associated with human exposure to toxic agrochemicals.

Hyaluronic Acid-Based Conjugates for Tumor-Targeted Drug Delivery and Imaging

In recent years, hyaluronic acid (HA) has attracted significant interest in development of drug delivery systems because of its intrinsic physicochemical and biological properties, including water solubility, viscoeleasticity, non-immunogenicity, biocompatibility, and biodegradability. In addition, HA has the ability to selectively bind specific receptors on the disease-related cells such as cancer cells and activated macrophages, followed by receptor-mediated endocytosis. Owing to these unique features, HA has been extensively used for development of the targetable carriers to deliver the therapeutic and imaging agents. In this review, we discuss the recent progress in various HA-based conjugates for cancer therapy and imaging, in which the active agents are covalently conjugated or physically encapsulated.

Hydrogels: a smart drug delivery device

Among various investigations hydrogels have attracted much attention Hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluid and swell. When swelled, they are soft & rubbery and resemble the living tissue. The various preparation techniques adopted are physical cross-linking, chemical cross-linking, grafting polymerization, and radiation cross-linking for the preparation of hydrogels. These biomaterials have gained attention owing to their peculiar characteristics like swelling in aqueous medium, pH and temperature sensitivity or sensitivity towards other stimuli. Hydrogels being biocompatible materials have been recognized to function as drug protectors, especially for peptides and proteins, from in-vivo environment. Also, these swollen polymers are helpful as targetable carriers for bioactive drugs with tissue specificity. Generally hydrogels are characterized for their morphology, swelling property, chemical structure and rheology. Morphological studies performed by using scanning electron microscopy (SEM) give us information about porous structure of hydrogels. Swelling determines the release mechanisms of the drug from the swollen polymeric mass while rheology give information about hydrogels.The hydrogels have been used extensively in various biomedical applications, viz. drug delivery, cell carriers and/or entrapment, wound management and tissue engineering. This article has been devoted to study the common methods of preparation, characterization, and application of hydrogels.

Simple small molecule carbon source strategy for synthesis of functional hydrothermal carbon: preparation of highly efficient uranium selective solid phase extractant

In this paper, simple small molecules, glyoxal and acrylonitrile, are chosen as starting materials to prepare an amidoxime-functionalized hydrothermal carbon-based solid phase extractant (HTC-AO) via a one-step hydrothermal process following a simple oximation. The resulting HTC-AO exhibits the anticipated properties, i.e., low porosity (0.01 cm3 g−1) and intraparticle diffusion coefficient (kint = 0.042 mmol g−1 min−0.5), high content of amidoxime groups (1.66 mmol g−1) and minimal undesired functional groups (typically carboxylic group: 0.07 mmol g−1; phenolic group: 0.38 mmol g−1; lactonic group: 0.01 mmol g−1). Moreover, the results of irradiation experiments under γ-ray dosages between 1 and 100 kGy indicate that HTC-AO has good radiation stability. The sorption behavior of U(VI) onto HTC-AO is investigated in detail using batch sorption experiments. A saturation U(VI) sorption capacity over that of all the uranium sorbents reported previously is found to be 1021.6 mg g−1 at pH 4.5 in single uranium solution, and a so far unreported highest uranium selectivity of 81.6% with a sorption capacity of 268.9 mg g−1 is observed at pH 2.5 in multi-ion solution. The significant outcomes in this work confirms that the “simple small molecule carbon source” strategy is practical and efficient, and may have the potential for the preparation of other types of functional materials such as highly specific catalysts, drug targeting carriers and others.

Polymersomes conjugated with des-octanoyl ghrelin for the delivery of therapeutic and imaging agents into brain tissues

The effective protection of the blood–brain barrier (BBB) from tight junctions and efflux transport systems ultimately results in the limited entry of 95% of drug/gene candidates, which are potentially beneficial for central nervous system (CNS) diseases. In order to enhance the brain-specific delivery, in this study we developed a targeting carrier system, which consists of poly(carboxyl ethylene glycol-g-glutamate)-co-poly(distearin-g-glutamate) (CPEGGM-PDSGM) polymersomes with the conjugation of des-octanoyl ghrelin. Des-octanoyl ghrelin across the BBB was reported to be unidirectional (blood-to-brain direction). However, there is no report about the conjugation of des-octanoyl ghrelin to a drug carrier system to confer the BBB targeting property through des-octanoyl ghrelin binding sites mediated endocytosis. To qualitatively and quantitatively investigate this carrier's properties, coumarin 6, Cy5.5 and met-enkephalin were individually encapsulated in these polymersomes. The experimental results showed that the cellular uptake was significantly higher for des-octanoyl ghrelin-conjugated polymersomes (GPs) than unconjugated polymersomes when co-incubated with the BBB cells. In addition, an enhanced accumulation in brain together with a reduced accumulation in liver and spleen was observed in animal study, indicating better brain selectivity for the GPs. In a hot-plate test, a significant inhibition of nociceptive response could be achieved for an intravenous injection of GPs encapsulated with met-enkephalin. The overall results demonstrated that GPs own a great potential for targeting delivery of drug across the BBB to treat CNS diseases.