Preparation of a novel chloromethylated polystyrene-2-mercapto-1,3,4-thiadiazole chelating resin and its adsorption properties and mechanism for separation and recovery of Hg(II) from aqueous solutions.

With an efficient methodology, a novel chloromethylated polystyrene-g-2-mercapto-1,3,4-thiadiazole chelating resin (MTR resin) was prepared via a one-step reaction. The structure of MTR resin was characterized by elements analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Meanwhile, the adsorption properties of the resin for Hg(II) were investigated by batch and column experiments. The results showed that the resin possessed much better adsorption capability for Hg(II) than for other metal ions. The statically and the dynamic saturated adsorption capacities were 343.8 mg/g and 475.1 mg/g. The adsorption kinetic and equilibrium data were well fitted to the second-order model and the Langmuir isotherm model, respectively. Desorption of mercury from the resin can be achieved using 30 mL of 2 mol/L HCl-5% thiourea solution with a desorption ratio of 92.3%. Compared with other absorbents, MTR resin was greatly conserve natural resources and reduce the cost.

Maltodextrin-Conjugated Gd-Based MRI Contrast Agents for Specific Diagnosis of Bacterial Infections.

Bacterial infections are one of the most serious health risks worldwide, and their rapid diagnosis remains a major challenge in clinic. To enhance the relaxivity and bacterial specificity of magnetic resonance imaging (MRI) contrast agents, here, a kind of gadolinium-based nanoparticles (NPs) of impressive biocompatibility is constructed as a contrast agent for maltodextrin-mediated bacteria-targeted diagnosis. To realize this, positively charged ultrasmall gadolinium oxide (Gd2O3, 2-3 nm) NPs are embedded in mesoporous silica NPs (MSN) with pore size around 6.38 nm. The resulting Gd2O3@MSN exhibits enhanced r1 value and T1-weighted MRI performance. Interestingly, upon conjugation of Gd2O3@MSN with maltodextrin to produce Gd2O3@MSN-Malt NPs, a remarkable decrease in internalization by osteosarcoma cells, alongside an increased adsorption toward E. coli and S. aureus, is achieved. It is therefore conceivable that the bacteria-targeted Gd2O3@MSN-Malt might be a promising MRI contrast agent for effective discrimination of bacterial infections from tumor.

Metal-Free Organo-Theranostic Nanosystem with High Nitroxide Stability and Loading for Image-Guided Targeted Tumor Therapy.

The desire for all-organic-composed nanoparticles (NPs) of considerable biocompatibility to simultaneously diagnose and treat cancer is undeniably interminable. Heretofore, metal-based agents dominate the landscape of available magnetic resonance imaging (MRI) contrast agents and photothermal therapeutic agents, but with associated metal-specific downsides. Here, an all-organic metal-free nanoprobe, whose appreciable biocompatibility is synergistically contributed by its tetra-organo-components, is developed as a viable alternative to metal-based probes for MRI-guided tumor-targeted photothermal therapy (PTT). This rationally entails a glycol chitosan (GC)-linked polypyrrole (PP) nanoscaffold that provides abundant primary and secondary amino groups for amidation with the carboxyl groups in a nitroxide radical (TEMPO) and folic acid (FA), to obtain GC-PP@TEMPO-FA NPs. Advantageously, the appreciably benign GC-PP@TEMPO-FA features high nitroxide loading (r1 = 1.58 mM-1 s-1) and in vivo nitroxide-reduction resistance, prolonged nitroxide-systemic circulation times, appreciable water dispersibility, potential photodynamic therapeutic and electron paramagnetic resonance imaging capabilities, considerable biocompatibility, and ultimately achieves a 17 h commensurate MRI contrast enhancement. Moreover, its GC component conveys a plethora of PP to tumor sites, where FA-mediated tumor targeting enables substantial NP accumulation with consequential near-complete tumor regression within 16 days in an MRI-guided PTT. The present work therefore promotes the engineering of organic-based metal-free biocompatible NPs in synergism, in furtherance of tumor-targeted image-guided therapy.

Synergistic triple-combination therapy with hyaluronic acid-shelled PPy/CPT nanoparticles results in tumor regression and prevents tumor recurrence and metastasis in 4T1 breast cancer.

Breast cancer is characterized by high aggression, poor prognosis, and high recurrence rate. Early detection and specific targeted treatment with less toxicity are the ultimate goals for breast cancer therapy. To improve antitumor therapeutic effects, we developed a novel polypyrrole nanoparticle using the near infrared dye IRDye800CW with camptothecin (CPT)-conjugated hyaluronic acid (HA) shell (PPy@CPT-HA-IRDye800CW) and performed a photothermal therapy (PTT), along with chemotherapy, guided by fluorescence and photoacoustic dual-modality imaging, in combination with immunotherapy. Irradiation with near infrared (NIR) light offered a strong PTT effect and promoted CPT drug release in tumors. Moreover, we found that chemo-photothermal therapy with PPy@CPT-HA-IRDye800CW NPs, in combination with immune checkpoint inhibitor anti-PD-L1 immunotherapy, synergistically enhanced the anti-tumor immune response, thereby eliminating primary breast cancer and preventing tumor metastases and recurrences in 4T1 tumor-bearing mice. This approach may provide important clues for the clinical management of breast cancer and other malignant tumors.

A pH-sensitive polymer based precise tumor targeting strategy with reduced uptake of nanoparticles by non-cancerous cells.

Drug-loaded nanoparticles can be specifically uptaken by tumor cells to realize active targeting due to the conjugated ligands or antibodies on their surface. However, some non-cancerous cells express non-specific receptors or antigens on their surface, which can react with the ligands or antibodies conjugated on the nanoparticle surface and then result in non-specific uptake of the nanoparticles by non-cancerous cells. In order to reduce the non-specific uptake of nanoparticles by non-cancerous cells, in this study, we proposed a pH-sensitive polymer based precise tumor targeting strategy and synthesized superparamagnetic iron oxide nanoparticle (SPION) encapsulated albumin nanoparticles (AN) with conjugation of folic acid (FA) and mPEG-DCA (SPION-AN-FA@mPEG), in which mPEG can shield FA, avoiding the non-specific recognition by normal cells under physiological conditions, and can be shed to expose FA in tumor microenvironments. The pH-sensitivity of mPEG-DCA was verified by HPLC characterization and 1H-NMR spectroscopy. The graft density and length of mPEG-DCA were optimized via the cellular uptake of SPION-AN-FA@mPEG measured by flow cytometry analysis. The r2 value and r2/r1 ratio of the optimized SPION-AN-FA@mPEG (i.e., SPION-AN-FA@mPEG4) are 168.6 mM-1 s-1 and 42.8, respectively, which are both much higher than that of the commercial contrast agent Resovist®. The in vitro T2-weighted MR images and in vivo MRI performance demonstrate that our SPION-AN-FA@mPEG4 nanoparticles can be used as an effective T2-weighted MRI contrast agent.

Preparation, physicochemical characterization and cytotoxicity in vitro of gemcitabine-loaded PEG-PDLLA nanovesicles.

AIM: To investigate the preparation, physicochemical characterization and cytotoxicity in vitro of Gemcitabine-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PDLLA) nanovesicles. METHODS: The nanovesicle carriers were prepared from the amphiphilic block copolymer of PEG-PDLLA by a double emulsion technique, and gemcitabine was used as the model drug. The morphology of the nanovesicles was determined by scanning and transmission electron microscopy, and the drug content, drug entrapment and drug-release curve in vitro were detected by UV-Vis-NIR spectrophotometry. Cytotoxicity in the human pancreatic cancer cell line SW1990 was tested by 3-(4,5-dimethyl) ethiazole (MTT) assay. RESULTS: The gemcitabine-loaded nanovesicles were hollow nanospheres with a mean size of 200.6 nm, drug loading of 4.14% and drug embedding ratio of 20.54%. The nanovesicles showed excellent controlled release that was characterized by a fast initial release during the first 72 h, followed by a slower and continuous release. The MTT assay demonstrated that gemcitabine-loaded nanovesicles exhibited dose-dependent and time-delayed cytotoxicity in the human pancreatic cancer cell line SW1990. CONCLUSION: Gemcitabine-loaded PEG-PDLLA nanovesicles prepared by a double emulsion technique exhibited good performance for controlled drug release, and had similar cytotoxic activity to free gemcitabine.