Positively charged conjugated microporous polymers with antibiofouling activity for ultrafast and highly selective uranium extraction from seawater.

Uranium high-efficiency separation from seawater still has some obstacles such as slow sorption rate, poor selectivity and biofouling. Herein, we report a strategy for ultrafast and highly selective uranium extraction from seawater by positively charged conjugated microporous polymers (CMPs). The polymers are synthesized by Sonogashira-Hagihara cross-coupling reaction of 1,3-dibromo-5,5-dimethylhydantoin and 1,3,5-triethynylbenzene, and then modified with oxime and carboxyl via click reaction. The CMPs show an ultrafast sorption (0.46 mg g-1 day-1) for uranium, and possess an outstanding selectivity with a high sorption capacity ratio of U/V (8.4) in real seawater. The study of adsorption process and mechanism indicate that the CMPs skeleton exhibits high affinity for uranium and can accelerate the sorption, and uranium(VI) is adsorbed on the materials by the interaction of oxime/carboxyl ligands and hydantoin. Moreover, the material can be simply loaded onto the filter membrane, and shows remarkable antibiofouling properties against E. coli and S. aureus and excellent uptake capacity for uranium with low concentration in real seawater. This work may provide a promising approach to design adsorbents with fast adsorption rate, high selectivity and antibacterial activity, and expand the thinking over the development of novel and highly efficient adsorbents for uranium extraction from seawater.

Smart Oral Administration of Polydopamine-Coated Nanodrugs for Efficient Attenuation of Radiation-Induced Gastrointestinal Syndrome.

High-dose ionizing radiation can lead to death from the unrecoverable damage of the gastrointestinal tract, especially the small intestine. Until now, the lack of predilection for the small intestine and rapid clearance by digestive fluids limit the effects of conventional radioprotective formulations. Herein, an innovative radioprotective strategy is developed for attenuating gastrointestinal syndrome by smart oral administration nanodrugs. The nanodrug is first engineered by encapsulating thalidomide into chitosan-based nanoparticles, and then coated with polydopamine. The behaviors of gastric acid-resistance, and pH-switchable controlled release in the small intestine enhance the oral bioavailability of the pyroptosis inhibitor thalidomide. In a mouse model, nanodrugs demonstrate prolonged small intestinal residence time and accessibility to the crypt region deep in the mucus. Furthermore, the nanodrugs ameliorate survival rates of C57BL/6J mice irradiated by 14 Gy of subtotal body irradiation and also maintain their epithelial integrity. This work may provide a promising new approach for efficiently attenuating lethal radiation-induced gastrointestinal syndrome and add insights into developing nanodrug-based therapies with improved efficacy and minimum side effects.

Magnetofluorescent nanohybrid comprising polyglycerol grafted carbon dots and iron oxides: Colloidal synthesis and applications in cellular imaging and magnetically enhanced drug delivery.

Multifunctional nanohybrids are attracting increasing attention for potential biomedical applications such as bioimaging and drug delivery due to their combined advantages of individual components. However, challenges in the improvement of their synthesis and colloidal stability to facilitate practical biomedical applications still remain. In this work, we report an efficient synthetic approach to fabricate magnetofluorescent nanohybrid (IO-PG-CD) comprising fluorescent carbon dots (CDs) and magnetic iron oxide nanoparticles (IOs) through polyglycerol (PG) mediated covalent linkage in aqueous media. CDs and IOs are first grafted with PG layer, and then functionalized with carboxyl and amino groups, respectively. The resulting CD-PG-COOH and IO-PG-NH2 handled as simple chemical compounds are integrated through EDC/NHS crosslinking to obtain the desired IO-PG-CD nanohybrid. The unprecedented hydrophilicity of PG layer endows IO-PG-CD nanohybrid with excellent colloidal stability in various physiological media, facilitating biomedical applications in vitro and in vivo. IO-PG-CD nanohybrid exhibits low cytotoxicity and its uptake by cells can be obviously enhanced by external magnetic attraction. The internalized IO-PG-CD nanohybrid emits multicolor fluorescence as observed by confocal fluorescence microscopy, demonstrating much better photostability than the nanoparticle labeled with organic dye. Taking advantage of enormous chelating carboxyl groups on the surface of IO-PG-CD nanohybrid, platinum-based anticancer drug was loaded on the surface (IO-PG-CD/Pt) through complexation and delivered into cancer cells in a magnetically enhanced manner, killing the cancer cells efficiently in vitro. Moreover, in vivo cancer therapy indicates that the external magnetic attraction also obviously improves the anticancer efficacy of IO-PG-CD/Pt in HeLa subcutaneous xenografts.

Polyglycerol grafting and RGD peptide conjugation on MnO nanoclusters for enhanced colloidal stability, selective cellular uptake and cytotoxicity.

An efficient surface engineering strategy for MnO nanoparticles was developed to attain enhanced colloidal stability, selective uptake by and toxicity to specific cancer cells. Specifically, MnO nanoclusters prepared by polyol method were grafted with polyglycerol (MnO-PG), and then conjugated with arginine-glycine-aspartate peptide (MnO-PG-RGD) through stepwise organic reactions. The physicochemical properties of the surface engineered MnO nanoclusters were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, zeta potential, transmission electron microscopy and high-resolution transmission electron microscopy. The grafted PG layer not only largely enhanced the dispersibility and colloidal stability of MnO nanoclusters in physiological media, but also effectively inhibited non-specific cellular uptake of MnO-PG. MnO-PG-RGD was selectively taken up by human glioblastoma U87MG cells overexpressing αvß3 integrins through receptor-mediated endocytosis. The internalized MnO-PG-RGD was mainly located in the lysosomes of U87MG cells. The acidity of lysosomes accelerated Mn2+ ions releasing, which promoted intracellular oxidative stress and further led to cell damage and apoptosis. The results indicate that appropriate surface functionalization can enable MnO nanoparticles to act as a potential anticancer agent in addition to their MRI functionality.

Ultrasmall Hyperbranched Semiconducting Polymer Nanoparticles with Different Radioisotopes Labeling for Cancer Theranostics.

Exploiting ultrasmall nanoparticles as multifunctional nanocarriers labeled with different radionuclides for tumor theranostics has attracted great attention in past few years. Herein, we develop multifunctional nanocarriers based on ultrasmall hyperbranched semiconducting polymer (HSP) nanoparticles for different radionuclides including technetium-99m (99mTc), iodine-131 (131I), and iodine-125 (125I) labeling. SPECT imaging of 99mTc labeled PEGylated HSP nanoparticles (HSP-PEG) exhibit a prominent accumulation in two-independent tumor models including subcutaneously xenograft and patient derived xenograft model. Impressively, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), as tumor-vascular disrupting agent (VDA), significantly improves the tumor accumulation of 131I labeled HSP-PEG nanoparticles, further leading to the excellent inhibition of tumor growth after intravenous injection. More importantly, SPECT imaging of 125I labeled HSP-PEG indicates that ultrasmall HSP-PEG nanoparticles could be slowly excreted from the body of a mouse through urine and feces in 1 week and cause no obvious toxicity to treated mice from blood analysis and histology examinations. Our finding from the different independent tumor models SPECT imaging shows that HSP-PEG nanoparticles may act as multifunctional nanocarriers to deliver different radionuclides for monitoring the in vivo behaviors of nanoparticles and cancer theranostics, which will provide a strategy for cancer treatment.

Polyglycerol mediated covalent construction of magnetic mesoporous silica nanohybrid with aqueous dispersibility for drug delivery.

Construction of nanohybrids with chemical and colloidal stability is of great importance for the exploration of their potential applications in biomedical field. In this work, a versatile strategy based on polyglycerol (PG) mediated covalent linkage is developed to fabricate a core-satellite nanohybrid, termed MMSN, consisting of a mesoporous silica nanoparticle (MSN) as a core and many superparamagnetic iron oxide nanoparticles (SPION) on the outer surface. In this synthetic strategy, the PG grafted SPION is derivatized to convert partial periphery hydroxyl groups to carboxyl moieties, followed by attachment to aminated MSN through amide bonds. The PG layer accounting for ~17wt% of MMSN not only serves as a tether to connect the two nanoparticles but also greatly enhances the colloidal stability of the nanohybrid, resulting in no significant change in hydrodynamic diameter and zeta potential during four months. Taking advantage of the combined porosity and magnetic property of the nanohybrid, a photosensitizer chlorin e6 (Ce6) is loaded on MMSN and efficiently delivered into target cells under magnetic guidance, leading to an enhanced efficacy of photodynamic therapy (PDT). The versatile strategy presented here opens up a new route to rational design and fabrication of multifunctional nanohybrids for various biomedical purposes.

Cationic Polyarginine Conjugated Mesoporous Bioactive Glass Nanoparticles with Polyglycerol Coating for Efficient DNA Delivery.

Mesoporous bioactive glass (MBG) is a type of material with high biological activity and excellent biocompatibility. Because of its high specific surface area and adjustable surface morphology, MBG is usable for loading and delivering molecules. In our previous report, MBG particles were used as gene vectors and showed good transfection rate. In this paper, MBG, prepared through a sacrificial liquid template method in sol­gel process, was covered with polyglycerol (PG) and the resulting MBG-PG was further functionalized with octaarginine (Arg8. More specifically, MBG-PG-Arg8 particles were synthesized by PG functionalization of MBG through ring-opening polymerization of glycidol on the MBG surface, followed by multistep organic transformations (­OH→ ­OTs (tosylate)→ ­N3 in the PG layer and click conjugation of the Arg8 terminated with propargyl glycine. MBG-PG-Arg8 was successfully taken up by cells more efficiently due to the cellpenetrating property of Arg8, and thus showed higher plasmid DNA loading and cell transfection efficiency than MBG modified with amino groups. This novel arginine-functionalized MBG may be a good candidate as a vector for gene delivery with higher efficiency.