Ligand Decoration Research Articles

Engineered extracellular vesicles for combinatorial TNBC therapy: SR-SIM-guided design achieves substantial drug dosage reduction

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has no therapeutic targets, relies on chemotherapeutics for treatment, and is in dire need of novel therapeutic approaches for improved patient outcomes. Extracellular vesicles (EVs) serve as intercellular communicators and have been proposed as ideal drug delivery vehicles. Here, EVs were engineered with RNA nanotechnology to develop TNBC tumor inhibitors. Using super resolved-structured illumination microscopy, EVs were optimized for precise Survivin small interfering RNA (siRNA) conjugated to chemotherapeutics loading and CD44 aptamer ligand decoration, thereby enhancing specificity toward TNBC cells. Conventional treatments typically employ chemotherapy drugs gemcitabine (GEM) and paclitaxel (PTX) at dosages on the order of mg/kg respectively, per injection (intravenous) in mice. In contrast, engineered EVs encapsulating these drugs saw functional tumor growth inhibition at significantly reduced concentrations: 2.2μg/kg for GEM or 5.6μg/kg for PTX, in combination with 21.5μg/kg survivin-siRNA in mice. The result is a substantial decrease in the chemotherapeutic dose required, by orders of magnitude, compared with standard regimens. Invivo and invitro evaluations in a TNBC orthotopic xenograft mouse model demonstrated the efficacy of this decreased dosage strategy, indicating the potential for decreased chemotherapy-associated toxicity.

Chiral Ligand-Decorated Rhodium Nanoparticles Incorporated in Covalent Organic Framework for Asymmetric Catalysis.

While metal nanoparticles (NPs) have demonstrated their great potential in catalysis, introducing chiral microenvironment around metal NPs to achieve efficient conversion and high enantioselectivity remains a long-standing challenge. In this work, tiny Rh NPs, modified by chiral diene ligands (Lx) bearing diverse functional groups, are incorporated into a covalent organic framework (COF) for the asymmetric 1,4-addition reactions between arylboronic acids and nitroalkenes. Though Rh NPs hosted in the COF are inactive, decorating Rh NPs with Lx creates the active Rh-Lx interface and induces high activity. Moreover, chiral microenvironment modulation around Rh NPs by altering the groups on chiral diene ligands greatly optimizes the enantioselectivity (up to 95.6 % ee). Mechanistic investigations indicate that the formation of hydrogen-bonding interaction between Lx and nitroalkenes plays critical roles in the resulting enantioselectivity. This work highlights the significance of chiral microenvironment modulation around metal NPs by chiral ligand decoration for heterogeneous asymmetric catalysis.

Chiral Ligand‐Decorated Rhodium Nanoparticles Incorporated in Covalent Organic Framework for Asymmetric Catalysis

AbstractWhile metal nanoparticles (NPs) have demonstrated their great potential in catalysis, introducing chiral microenvironment around metal NPs to achieve efficient conversion and high enantioselectivity remains a long‐standing challenge. In this work, tiny Rh NPs, modified by chiral diene ligands (Lx) bearing diverse functional groups, are incorporated into a covalent organic framework (COF) for the asymmetric 1,4‐addition reactions between arylboronic acids and nitroalkenes. Though Rh NPs hosted in the COF are inactive, decorating Rh NPs with Lx creates the active Rh−Lx interface and induces high activity. Moreover, chiral microenvironment modulation around Rh NPs by altering the groups on chiral diene ligands greatly optimizes the enantioselectivity (up to 95.6 % ee). Mechanistic investigations indicate that the formation of hydrogen‐bonding interaction between Lx and nitroalkenes plays critical roles in the resulting enantioselectivity. This work highlights the significance of chiral microenvironment modulation around metal NPs by chiral ligand decoration for heterogeneous asymmetric catalysis.

Ligand Functionalization of Metal‐Organic Frameworks for Photocatalytic H2O2 Production

AbstractH2O2 production by photocatalysis has received considerable attention, while using MOF‐based materials as photocatalysts is still less explored. Ligand functionalization of MOFs is a decoration way at the molecular level, which provides the basis for the further modification of MOFs. In this concept, ligand functionalization of MOFs for photocatalytic H2O2 production has been systematically and extensively discussed. The strategies of ligand functionalization include grafting of functional groups (e. g. amino, methoxyl, boron and alkyl) and multiple ligand decoration. Correspondingly, some specific effects are achieved, e. g. improved charge carrier separation, enhanced O2 adsorption and hydrophobicity, which can realize efficient H2O2 production by photocatalysis. Meanwhile, reaction conditions and activities of photocatalytic H2O2 production have also been explicitly introduced in these studies. At last, the future perspectives are proposed. This concept sheds fresh light on the great potential of ligand functionalization of MOFs for photocatalytic H2O2 production.

Aging CsPbBr3 Nanocrystal Wafer for Ultralow Ionic Migration and Environmental Stability for Direct X-ray Detection.

The outstanding photoelectric properties of perovskites demonstrate extreme promise for application in X-ray detection. However, the soft lattice of the perovskite results in severe ionic migration for three-dimensional materials, limiting the operation stability of perovskite X-ray detectors. Although ligand-decorated nanocrystals (NCs) exhibit significantly higher stability than three-dimensional perovskites, defects remaining on the interface of NCs could still trigger halide migration under a high bias due to the incomplete ligand decoration. Furthermore, it is still challenging to realize sufficient thickness of absorption layers based on NCs for X-ray detectors through traditional methods. Herein, we develop a centimeter-size and millimeter-thick wafer based on CsPbBr3 NCs through isostatic pressing for X-ray detectors, in which the interfacial defects of NCs are remedied by CsPb2Br5 during aging of wafer in ambient humidity. The wafer shows outstanding sensitivity (200 μC Gyair-1 cm-2) and ultralow dark current drift (1.78 × 10-8 nA cm-1 s-1 V-1 @ 400 V cm-1). Moreover, it shows storage stability with negligible performance degradation for 60 days in ambient humidity. Thus, aging perovskite NC wafers for X-ray detection holds huge potential for next-generation X-ray imaging plates.

Galactose Tethered Decellularized Liver Matrix: Toward a Biomimetic and Biofunctional Matrix for Liver Tissue Engineering.

The major challenge in liver tissue engineering is the replication of the microenvironment and microarchitecture of the liver tissue at the nanoscale. Decellularized liver matrix (DLM) provides an ideal material for scaffold preparation, as it retains the relevant structural and biochemical composition. However, the loss of bioactive factors during decellularization needs to be taken into account when using DLM and should be supplemented accordingly for an expected outcome. This study reports on the modification of DLM by the addition of galactose residues using a two-step thiol-ene-mediated photoclick chemistry for the coupling of galactose moieties to the DLM. Modification with galactose enhanced the function of hepatocytes and provides many advantages over currently used DLM and DLM-based materials. The galactose modified DLM enhanced the initial HepG2 cell adhesion to the substrate with changes in dynamics over time such as spheroid formation and further migration on the matrix. Our observation is that the galactose ligand decoration can also enhance the liver-specific metabolism of HepG2 compared to unmodified DLM. Galactosylated DLM also showed a better establishment of cellular polarity which also contributes to the function of HepG2 cells. Together our results demonstrate the advantages of adding galactose residues to currently available biomaterials, which makes this approach an attractive method for ECM-based liver tissue engineering.

Second harmonic scattering multipole analysis of ligand-decorated gold nanoparticles

Ligand decoration of noble metallic nanoparticles is often needed for some applications, such as biochemical sensing, catalysis and nanotechnology, and the understanding of its process is of great importance. The second harmonic scattering (SHS) technique with advantages of surface-sensitivity and label-free detection, provides intrinsic information for such a research. In this work, the second harmonic(SH) scattering patterns of two types of ligands (cetyltrimethylammonium chloride and L-cysteine) capped gold nanoparticles (GNPs) with the same radii are measured. Both the intensities and shapes of the SH scattering patterns are changed after the ligand exchange process. In order to explain the pattern changes, the analytic expressions of SH scattering are derived theoretically for a relatively large nanoparticle based on Dadap’s multipolar theory. Considering the derived relationship between the multipole (up to octopole) contributions and the power of the nanosphere radius, the effective size effect is introduced to express the SH scattering signal change for different ligand decorations and well explain the experimental results. This theory provides a new perspective of the SH scattering response to different capping ligands and offers a possible quantitative method to analyze interface physical chemistry for ligands on the surface of nanoparticles.

A common strategy to improve transmembrane transport in polarized epithelial cells based on sorting signals: Guiding nanocarriers to TGN rather than to the basolateral plasma membrane directly

The intestinal barrier has always been the rate-limiting step in the oral administration process. To overcome the intestinal barrier, researchers have widely adopted nanocarriers, especially active-targeting nanocarriers strategies. However, most of these strategies focus on the ligand decoration of nanocarriers targeting specific receptors, so their applications are confined to specific receptors or specific cell types. In this study, we tried to investigate more common strategies in the field of transmembrane transport enhancement. Trans-Golgi network (TGN) is the sorting center of biosynthetic route which could achieve polarized localization of proteins in polarized epithelial cells, and the basolateral plasma membrane is where all transcytotic cargos have to pass through. Thus, it is expected that guiding nanocarriers to TGN or basolateral plasma membrane may improve the transcytosis. Hence, we choose sorting signal peptide to modify micelles to guide micelles to TGN (named as BAC decorated micelles, BAC-M) or to basolateral plasma membrane (named as STX decorated micelles, STX-M). By incorporating coumarin-6 (C6) or Cy5-PEG-PCL in the micelles to indicate the behavior of micelles, the effects of these two strategies on the transcytosis were investigated. To our surprise, BAC-M and STX-M behaved quite differently when crossing biological barriers. BAC-M showed significant superiority in colocalization with TGN, transmembrane transport and even in vivo absorption, while STX-M had no significant difference from blank micelles. Further investigation revealed that the strategy of directly guiding nanocarriers to the basolateral plasma membrane (STX-M) only caused the stack of vesicles near the basolateral plasma membrane. So, we concluded that guiding nanocarriers to TGN which related to secretion may contribute to the transmembrane transport. This common strategy based on the physiological function of TGN in polarized epithelial cells will have broad application prospects in overcoming biological barrier.

Polymeric Nanoparticles for Mitochondria Targeting Mediated Robust Cancer Therapy.

Despite all sorts of innovations in medical researches over the past decades, cancer remains a major threat to human health. Mitochondria are essential organelles in eukaryotic cells, and their dysfunctions contribute to numerous diseases including cancers. Mitochondria-targeted cancer therapy, which specifically delivers drugs into the mitochondria, is a promising strategy for enhancing anticancer treatment efficiency. However, owing to their special double-layered membrane system and highly negative potentials, mitochondria remain a challenging target for therapeutic agents to reach and access. Polymeric nanoparticles exceed in cancer therapy ascribed to their unique features including ideal biocompatibility, readily design and synthesis, as well as flexible ligand decoration. Significant efforts have been put forward to develop mitochondria-targeted polymeric nanoparticles. In this review, we focused on the smart design of polymeric nanosystems for mitochondria targeting and summarized the current applications in improving cancer therapy.

Fine-Tuning Apertures of Metal-Organic Cages: Encapsulation of Carbon Dioxide in Solution and Solid State.

Metal-organic cages are potential artificial models for mimicking biological functions due to their capability of selective encapsulation for certain guest molecules. In this work, we designed and synthesized a series of rhombic dodecahedral Ni-imidazolate cages (Ni14L24) with precisely controlled aperture for CO2 encapsulation. The aperture of the cages can be tuned by the strategies of ligand decoration and metal-ion hybridization. Similar to the breathing function of alveoli, CO2 passes through the dynamic aperture into the cages under a pressure of 2.0-3.0 bar in methanol solution, and slowly move out of the cages when the pressure goes down. In the solid state, CO2 is encapsulated and prisoned in the cages under a high pressure of 15.0-30.0 bar or supercritical conditions. By replacing the square-coordinated Ni2+ with Cu2+, the resulting Ni-Cu heteronuclear cage lost the capability of physically encapsulating CO2 even though the aperture's size is only slightly changed.

Use of Polymeric Nanoparticle Platform Targeting the Liver To Induce Treg-Mediated Antigen-Specific Immune Tolerance in a Pulmonary Allergen Sensitization Model.

Nanoparticles (NPs) can be used to accomplish antigen-specific immune tolerance in allergic and autoimmune disease. The available options for custom-designing tolerogenic NPs include the use of nanocarriers that introduce antigens into natural tolerogenic environments, such as the liver, where antigen presentation promotes tolerance to self- or foreign antigens. Here, we demonstrate the engineering of a biodegradable polymeric poly(lactic- co-glycolic acid) (PLGA) nanocarrier for the selective delivery of the murine allergen, ovalbumin (OVA), to the liver. This was accomplished by developing a series of NPs in the 200-300 nm size range as well as decorating particle surfaces with ligands that target scavenger and mannose receptors on liver sinusoidal endothelial cells (LSECs). LSECs represent a major antigen-presenting cell type in the liver capable of generating regulatory T-cells (Tregs). In vitro exposure of LSECs to NPOVA induced abundant TGF-β, IL-4, and IL-10 production, which was further increased by surface ligands. Animal experiments showed that, in the chosen size range, NPOVA was almost exclusively delivered to the liver, where the colocalization of fluorescent-labeled particles with LSECs could be seen to increase by surface ligand decoration. Moreover, prophylactic treatment with NPOVA in OVA-sensitized and challenged animals (aerosolized inhalation) could be seen to significantly suppress anti-OVA IgE responses, airway eosinophilia, and TH2 cytokine production in the bronchoalveolar lavage fluid. The suppression of allergic airway inflammation was further enhanced by attachment of surface ligands, particularly for particles decorated with the ApoB peptide, which induced high levels of TGF-β production in the lung along with the appearance of Foxp3+ Tregs. The ApoB-peptide-coated NPs could also interfere in allergic airway inflammation when delivered postsensitization. The significance of these findings is that liver and LSEC targeting PLGA NPs could be used for therapy of allergic airway disease, in addition to the potential ofusing their tolerogenic effects for other disease applications.

Lipopepsomes: A novel and robust family of nano-vesicles capable of highly efficient encapsulation and tumor-targeted delivery of doxorubicin hydrochloride in vivo

Doxil® is the first FDA-approved anti-cancer nano-drug. Notably, no targeted liposomal formulation has advanced to clinical stage despite tremendous work undertaken, partly due to a low stability of liposomes. Here, we report on novel lipopepsomes self-assembled from poly(ethylene glycol)-b-poly(α-aminopalmitic acid) as a stable and versatile alternative to liposomes for highly efficient encapsulation and tumor-targeted delivery of doxorubicin hydrochloride (Dox·HCl). Interestingly, lipopepsomes could be easily decorated with 20mol% cRGD peptide and loaded with 17.4wt% Dox·HCl, giving cRGD-LPP-Dox with a small size of ~80nm. cRGD-LPP-Dox exhibited a high stability against 10% FBS and restrained drug release under physiological conditions. Flow cytometry, confocal microscopy and MTT assays using αvβ3–overexpressing A549 tumor cells showed obviously more efficient uptake and higher anticancer activity for cRGD-LPP-Dox than for non-targeted LPP-Dox and clinically used liposomal Dox (Lipo-Dox) controls. Notably, cRGD-LPP-Dox exhibited markedly enhanced toleration and tumor accumulation than Lipo-Dox. The therapeutic studies demonstrated that cRGD-LPP-Dox achieved effective suppression of orthotopic A549 human lung tumor in nude mice, resulting in significantly improved survival rate as compared to LPP-Dox and Lipo-Dox groups. Lipopepsomes with small size, efficient loading of Dox·HCl, high stability and versatile ligand decoration have appeared as a highly attractive nanoplatform for targeted tumor chemotherapy.

Triol-Ligand Modification and Structural Transformation of Anderson-Evans Oxomolybdates via Modulating Oxidation State of Co-Heteroatom.

Various covalent decorations and structural transformations of a series of R-C(CH2OH)3 triol ligands on CoII/CoIII-centered Anderson-Evans polyoxomolybdates were studied in aqueous and/or organic solution. Single-crystal X-ray structural analysis demonstrated that four manners, including (1) double-sided χ/χ-isomer and (2) double-sided δ/χ-isomer with CoII central heteroatom, and (3) single-sided δ-isomer and (4) double-sided δ/δ-isomer with CoIII central heteroatom, appeared on the decoration of the mother polyanion [CoII/III(OH)6Mo6O18]4-/3-. Through careful manipulation of the reaction conditions, a gradual oxidation process from CoII to CoIII was disclosed to happen in air, and accompanying that process, the CoII-centered double-sided δ/χ-isomer that formed in the initial stage transformed into a CoIII-centered double-sided δ/δ-isomer. When the electron-withdrawing group -NO2 substituted triol ligand was used to replace CH3C(CH2OH)3, the oxidation process accelerated spontaneously. A further investigation showed that this oxidation process can be blocked by acid. While the triol ligands' decoration on Anderson-Evans polyoxometalates (POMs) took place along with the oxidation of the central heteroatom, that codecoration of other components was also accomplished. In the presence of excess acetic acid, an unprecedented single-sided δ-isomer with an acetate ligand covalently attaching on the other side by replacing one μ3-O atom was obtained in aqueous solution. The reaction of the mother cluster [(n-C4H9)4N]3[Co(OH)6Mo6O18] and triol ligands in methanol resulted in a codecoration of methanol with the double-sided δ/δ-isomer, which has never been reported in B-type Anderson-Evans POMs. The obtained results revealed that the oxidation state of the heteroatom has a significant impact on the triol ligand decoration styles, such as the χ/χ- or δ/χ-isomer for the divalent heteroatom and the δ- or δ/δ-isomer for the trivalent heteroatom.

Phosphine–Ligand Decoration toward Active and Robust Iron Catalysts in LRP

Phosphine ligands were designed to enhance the catalytic activity of iron(II) complexes [FeBr2(PR3)2] for metal-catalyzed living radical polymerization (LRP), and special efforts were directed to the improvement in catalytic activity and robustness against functional monomers. Introduction of an electron donating group {methoxy [P(MeOPh)3] or N,N′-dimethylamino [Ph2P(Me2NPh)]} onto the para position of triphenyl phosphine (PPh3) allowed active and robust Fe(II) complexes that catalyzed LRP of poly(ethylene glycol) methacrylate (PEGMA) smoothly proceeding to high conversion (∼90%), to form polymers of controlled molecular weights and its distributions (Mw/Mn < 1.2). In contrast, such an enhancement was absent with the parent ligand PPh3 and those with electron-withdrawing substituents. Furthermore, the replacement of the three methoxy groups in P(MeOPh)3 with PEG chains led to a more robust catalyst, especially tolerant of the hydroxyl group in 2-hydroxyethyl methacrylate (HEMA). Accordingly, this catalyst enabled a four-component random living copolymerization of HEMA, PEGMA, and two alkyl methacrylates, where all the monomers randomly copolymerized into statistical copolymers of controlled molecular weights.

Conducting the Temperature-Dependent Conformational Change of Macrocyclic Compounds to the Lattice Dilation of Quantum Dots for Achieving an Ultrasensitive Nanothermometer

We report a ligand decoration strategy to enlarge the lattice dilation of quantum dots (QDs), which greatly enhances the characteristic sensitivity of a QD-based thermometer. Upon a multiple covalent linkage of macrocyclic compounds with QDs, for example, thiolated cyclodextrin (CD) and CdTe, the conformation-related torsional force of CD is conducted to the inner lattice of CdTe under altered temperature. The combination of the lattice expansion/contraction of CdTe and the stress from CD conformation change greatly enhances the shifts of both UV-vis absorption and photoluminescence (PL) spectra, thus improving the temperature sensitivity. As an example, β-CD-decorated CdTe QDs exhibit the 0.28 nm shift of the spectra per degree centigrade (0.28 nm/°C), 2.4-fold higher than those of monothiol-ligand-decorated QDs.

In vitro and in vivo hemostatic capabilities of a functionally integrated platelet-mimetic liposomal nanoconstruct

There is significant clinical interest in synthetic platelet substitutes that can mimic platelet's hemostastic functionalities while allowing scale-up, minimal biological contamination, and long shelf-life. To this end, mimicking active platelet's hemostatically relevant matrix-adhesion properties and aggregation properties independently and then integrating them via heteromultivalent ligand decoration on a single synthetic particle can lead to an efficient platelet substitute design. We have recently reported on the feasibility of this approach in vitro, using liposomes as model particles. Building on these studies, here we demonstrate the capability of optimizing the platelet-mimetic properties of our liposomal constructs in vitro via modulating the ligand-decoration densities and ligand ratios. In addition, we demonstrate the enhanced hemostatic efficacy of the functionally-integrated platelet-mimetic constructs in vivo. Liposomes were surface-decorated with collagen- and VWF-binding peptides (CBP and VBP) to mimic platelet adhesion and a fibrinogen-mimetic peptide (FMP) to promote platelet aggregation. Modulation of VBP- and CBP-densities and relative ratios enabled optimizing construct adhesion under varying shear-flow conditions. Modulation of FMP-density enabled enhancement of construct-promoted platelet aggregation. The VBP-, CBP- and FMP-decorations were integrated on a single liposome, and these functionally-integrated constructs showed significantly higher hemostatic efficacy in vivo in a mouse tail-transection model compared to ‘adhesion-only’ or ‘aggregation-only’ constructs.

EGF Receptor-Targeted Nanocarriers for Enhanced Cancer Treatment

The 'nanomedicine' approach has revolutionized cancer therapy by enabling the packaging of therapeutic agents within engineered nanovehicles that can specifically accumulate within the tumor stroma and then be internalized within cancer cells, to render site-selective action while minimizing nonspecific uptake and harmful side effects. While the specific accumulation within the tumor stroma is rendered by the ability of the nanovehicles to passively permeate through the tumor's leaky vasculature, the cellular internalization is often achieved by exploiting receptor-mediated active endocytotic mechanisms using receptor-specific ligand decoration on the vehicle surface. To this end, a highly important receptor found in several cancers is the EGF receptor, which has been implicated in tumor aggression and proliferation. In this context, we provide a comprehensive review of the various approaches of ligand decorations on nanovehicles for active targeting to EGF receptors, and discuss their pros and cons towards optimizing the design of EGF receptor-targeted nanomedicine systems.

Demonstration of Ligand Decoration, and Ligand-Induced Perturbation, of G-Quadruplexes in a Plasmid Using Atomic Force Microscopy

G-Quadruplexes are nucleic acid secondary structures consisting of a planar arrangement of four guanine residues. Potential G-quadruplex-forming sequences are widely distributed throughout the genome. Significantly, they are present in telomeres and are enriched in gene promoters and first introns, raising the possibility that perturbation of G-quadruplex stability might have therapeutic potential, for example in the treatment of cancer. Ligands that interact selectively with G-quadruplexes include both proteins and small molecules, although the interactions between ligands and their G-quadruplex targets have been monitored using indirect methods. In addition, the G-quadruplex targets have often been short DNA fragments. Here, we have used atomic force microscopy imaging to examine directly at the single-molecule level the interaction of ligands with G-quadruplexes generated during transcription of a plasmid containing a G-rich insert. We show that the structures produced during transcription are decorated specifically by the single-chain antibody HF1 and by the nuclear protein PARP-1, both of which are known to recognize G-quadruplexes. Our results provide clear structural evidence of G-quadruplex formation in a transcription-dependent case and demonstrate directly how small-molecule stabilizers and destabilizers can manipulate these structures in a biochemically functional system.

Targeted CRM197-PEG-PEI/siRNA Complexes for Therapeutic RNAi in Glioblastoma.

RNA interference (RNAi) allows the specific knockdown of tumor relevant genes. To induce RNAi, the delivery of small interfering RNAs (siRNAs) is of crucial importance. This is particularly challenging for their therapeutic applications in vivo. Low molecular weight branched polyethylenimine (PEI) is safe and efficient for nucleic acid delivery including small RNA molecules, based on its ability to electrostatically complex siRNA molecules, thereby protecting them from nuclease degradation. The nanoscale PEI/siRNA complexes are endocytosed by cells prior to intracellular complex release from the lysosome and cytoplasmic release of the siRNAs from the complexes. Chemical modification and ligand decoration of the complexes aim at introducing target tissue specificity and further increased efficacy of PEI-mediated siRNA delivery. CRM197 is a mutated, non-toxic diphtheria toxin (DT) that binds to the membrane-bound precursor of HB-EGF-like growth factor/diphtheria toxin receptor highly expressed in glioblastoma cells. Likewise, the growth factor pleiotrophin (PTN/HB-GAM/HARP) is overexpressed in glioblastoma and is rate limiting for tumor growth, thus representing an attractive target gene for therapeutic knockdown approaches. PEGylation of PEI was performed to reduce the surface charge, and by CRM197 coupling we prepared a modified PEI for siRNA delivery into glioblastoma cells. The novel PEI conjugates were analyzed for their complexation efficiency and optimal mixing ratios, and complexes were physicochemically characterized regarding stability, size and zeta potential. The biological activity of the complexes was confirmed in cell culture by reporter gene knockdown. For the therapeutic treatment of subcutaneous human gliobastoma xenografts in athymic nude mice, we systemically injected the modified PEI/siRNA complexes targeting PTN. Antitumor effects based on PTN knockdown demonstrated the advantage of tumor-targeted CRM197-PEG-PEI/siRNA over untargeted PEG-PEI polyplexes. Thus, we establish targeted CRM197-PEG-PEI-based complexes for siRNA delivery in vivo, and show therapeutic effects of CRM197-PEG-PEI/siRNA-mediated knockdown of PTN.

Fine-tuning of lanthanide-monocarboxylate coordination networks through ligand decoration

We report herein five new coordination polymers of general formula [LnNa(C(6)H(5)CO(2))(4)] where Ln = Y (6), Tb (7), Er (8), [DyNa(CH(3)CO(2))(4)(MeOH)] (9) and [DyNa(C(3)H(7)CO(2))(4)] (10). Single crystal structure analyses revealed that all compounds have a repeating unit containing one Ln(3+), one Na(+) and four monocarboxylate ligands (RCO(2)(-)) (R = -CH(3), -C(3)H(7), -C(6)H(5)). Compounds 6-8 and 10 possess helical polymeric structures which are extended in three dimensions forming chiral srs networks whilst compound 9 constitutes a two dimensional honeycomb network, illustrating that variation in the alkyl group of the monocarboxylate can result in versatile and variable polymeric networks. The magnetic properties of the reported compounds have also been studied.