Biocompatible Ligand Research Articles

(Invited) Synthetic Strategies to Lower the Barrier for Making High Quality Quantum Dot Probes

Quantum dot (QD)-based bioimaging requires QDs with exceptional optical quality and well-controlled surface properties. Although extensive research has been carried out to produce high-quality nanocrystals and to design biocompatible ligands, significant expertise is required to synthesize the best quality QDs and ligands reported. Commercially available QDs often fail to meet the required quality and suffer from irreproducibility in their performance. These restrictions have limited the wide adoption of QDs for biomedical imaging in non-expert groups. My group strives to lower the barrier to preparing high-quality QD probes in a wide range of wavelengths. In this talk, I will discuss the synthetic strategies that we have developed to systematically grow high-quality nanocrystals of various sizes and materials with minimal human intervention and simplify the synthesis of polyimidazole ligands without compromising their quality. By lowering the synthetic barrier to high-quality QDs, we envision unleashing the full potential of QDs in various fields.

Superparamagnetic iron oxide nanoparticles functionalized by biocompatible ligands with enhanced high specific absorption rate for magnetic hyperthermia

This study introduces a novel green nanocomposite system of iron oxide coated with secondary metabolites (Fe3O4@SM) and compares it with commonly used materials for hyperthermia cancer treatment. Fe3O4@SM magnetic nanoparticles were synthesized through a simple co-precipitation process using metal precursors, followed by heating in pressure reactor to obtain superparamagnetic nanoparticles (Hc = 36.5–54.1 Oe at 300 K). These nanoparticles were subsequently coated with plant-based phytochemicals. XRD analysis confirmed the presence of magnetite iron oxide nanoparticles. SEM images further confirmed the spherical shape of the synthesized nanoparticles, exhibiting a face-centered cubic (FCC) iron oxide structure with sizes ranging from 12±7–85±15 nm. Characterization through dynamic light scattering (DLS) and zeta potential (ζ) analysis demonstrated colloidal stability, with a polydispersity index (PDI) ranging from 0.226 to 0.436 and zeta potential values ranging from −29.761–1.85 mV. The surface of the nanoparticles was analyzed using GC-MS, which identified bioactive functional groups including ester (42.79 %), terpene (20.69 %), hydrocarbons (17.4 %), and carboxylic (12.37 %) compounds. Compared to Fe3O4 and Fe3O4@GO, Fe3O4@SM exhibited a higher rate of temperature increase within the therapeutic range, reaching Tmax = 45°C with a heating rate (dT/dt) of 0.273 °C/s and specific absorption rate (SAR) of 230.6 W/g at 304 kHz and 400 Oe. In vitro assays utilizing a triple negative breast cancer microenvironment confirmed the non-toxicity of these materials through a DNS assay. The developed nanoparticles offer dual mechanisms of action, combining thermal and chemo effects, making them promising candidates for hyperthermia cancer treatment.

Biomimetic Chiral Nanomaterials with Selective Catalysis Activity.

Chiral nanomaterials with unique chiral configurations and biocompatible ligands have been booming over the past decade for their interesting chiroptical effect, unique catalytical activity, and related bioapplications. The catalytic activity and selectivity of chiral nanomaterials have emerged as important topics, that can be potentially controlled and optimized by the rational biochemical design of nanomaterials. In this review, chiral nanomaterials synthesis, composition, and catalytic performances of different biohybrid chiral nanomaterials are discussed. The construction of chiral nanomaterials with multiscale chiral geometries along with the underlying principles for enhancing chiroptical responses are highlighted. Various biochemical approaches to regulate the selectivity and catalytic activity of chiral nanomaterials for biocatalysis are also summarized. Furthermore, attention is paid to specific chiral ligands, materials compositions, structure characteristics, and so on for introducing selective catalytic activities of representative chiral nanomaterials, with emphasis on substrates including small molecules, biological macromolecule, and in-site catalysis in living systems. Promising progress has also been emphasized in chiral nanomaterials featuring structural versatility and improved chiral responses that gave rise to unprecedented chances to utilize light for biocatalytic applications. In summary, the challenges, future trends, and prospects associated with chiral nanomaterials for catalysis are comprehensively proposed.

Redox nanodrugs alleviate chronic kidney disease by reducing inflammation and regulating ROS.

Immune-mediated glomerular diseases lead to chronic kidney disease (CKD), primarily through mechanisms such as immune cell overactivation, mitochondrial dysfunction and imbalance of reactive oxygen species (ROS). We have developed an ultra-small nanodrug composed of Mn3O4 nanoparticles which is functionalized with biocompatible ligand citrate (C-Mn3O4 NPs) to maintain cellular redox balance in an animal model of oxidative injury. Furthermore, this ultra-small nanodrug, loaded with tacrolimus (Tac), regulated the activity of immune cells. We established a doxorubicin (DOX)-induced CKD model in SD rats using conditions of oxidative distress. The results demonstrate the ROS scavenging capability of Mn3O4 NPs, which mimics enzymatic activity, and the immunosuppressive effect of tacrolimus. This combination promotes targeted accumulation in the renal region with sustained drug release through the enhanced permeability and retention (EPR) effect. Tac@C-Mn3O4 protects the structural and functional integrity of mitochondria from oxidative damage while eliminating excess ROS to maintain cellular redox homeostasis, thereby suppressing the overexpression of pro-inflammatory cytokines to restore kidney function and preserve a normal kidney structure, reducing inflammation and regulating antioxidant stress pathways. This dual-pronged treatment strategy also provides novel strategies for CKD management and demonstrates substantial potential for clinical translational application.

Glycosyl Triazole Based Pyridinamide/CuI-Catalyzed Coupling of 2-Halobenzamides with Active Methylene Compounds

AbstractThis report describes a convenient method for the Cu(I)-catalyzed tandem synthesis of dihydrophenanthridinediones and substituted isoquinolinones with the assistance of efficient glycosyl 1,2,3-triazole-based pyridinamide ligands. The catalytic system effectively works for the coupling of N-substituted 2-halobenzamides with various active methylene compounds to form biologically relevant heterocyclic scaffolds in high to excellent yields. The consecutive path of the reaction including intermolecular C–C cross-coupling followed by intramolecular cyclization efficiently takes place at low catalytic loading. These glycosyl triazole-appended pyridinamides were synthesized in good yields by a CuI/DIPEA-mediated regioselective CuAAC click reaction. The notable features of the method include low catalytic loading, the use of cost-effective and biocompatible ligands, high reaction yield, and easily accessible starting materials that make the protocol more versatile.

Triazole-Appended Glycohybrid/CuI-Catalyzed C-C Cross-Coupling of Aryl/Heteroaryl Halides with Alkynyl Sugars.

This report describes a convenient method for the Cu(I)-catalyzed Sonogashira cross-coupling reaction of aryl/heteroaryl halides and alkynyl sugars in the presence of a 1,2,3-triazole-appended glycohybrid as a biocompatible ligand. The Sonogashira cross-coupling products were exclusively formed without the Glaser-Hay homocoupling reaction in the presence of a glycosyl monotriazolyl ligand at 120 °C. However, the Glaser-Hay homocoupling products were obtained at 60-70 °C in the presence of bis-triazolyl-based macrocyclic glycohybrid ligand L8. The glycosyl triazole ligands were synthesized via the CuI/DIPEA-mediated regioselective CuAAC click reaction, and a series of glycohybrids of glucose, mannose, and galactose alkynes including glycosyl rods were developed in good yields. The developed glycohybrids have been well characterized by various spectroscopic techniques, such as nuclear magnetic resonance, high-resolution mass spectrometry, and single-crystal X-ray data of L3. The protocol works well with the heteroaryl and naphthyl halides, and the mechanistic approach leads to CuI/ligand-assisted oxidative coupling. The coupling protocol has notable features, including low catalytic loading, cost-effectiveness, biocompatible nature, and a wide substrate scope.

Magnetic Nanoparticle-Based High-Performance Positive and Negative Magnetic Resonance Imaging Contrast Agents.

In recent decades, magnetic nanoparticles (MNPs) have attracted considerable research interest as versatile substances for various biomedical applications, particularly as contrast agents in magnetic resonance imaging (MRI). Depending on their composition and particle size, most MNPs are either paramagnetic or superparamagnetic. The unique, advanced magnetic properties of MNPs, such as appreciable paramagnetic or strong superparamagnetic moments at room temperature, along with their large surface area, easy surface functionalization, and the ability to offer stronger contrast enhancements in MRI, make them superior to molecular MRI contrast agents. As a result, MNPs are promising candidates for various diagnostic and therapeutic applications. They can function as either positive (T1) or negative (T2) MRI contrast agents, producing brighter or darker MR images, respectively. In addition, they can function as dual-modal T1 and T2 MRI contrast agents, producing either brighter or darker MR images, depending on the operational mode. It is essential that the MNPs are grafted with hydrophilic and biocompatible ligands to maintain their nontoxicity and colloidal stability in aqueous media. The colloidal stability of MNPs is critical in order to achieve a high-performance MRI function. Most of the MNP-based MRI contrast agents reported in the literature are still in the developmental stage. With continuous progress being made in the detailed scientific research on them, their use in clinical settings may be realized in the future. In this study, we present an overview of the recent developments in the various types of MNP-based MRI contrast agents and their in vivo applications.

Self‐Fluorescent Reactive Oxygen Species‐Responsive Zinc(II)‐Quinoline Module Functionalized Polycations Hold Great Potentials in siRNA‐Mediated Gene Therapy

AbstractA novel quinoline‐based thioketal‐containing zinc (II) coordinative module (Zn‐QS) is designed to transform common low‐molecular‐weight (LMW) polyethyleneimine (PEI) into a high‐performance siRNA carrier (Zn‐PQ) with self‐fluorescence and reactive oxygen species (ROS)‐responsiveness. In the multifunctional module, a quinoline derivative, frequently serving as pharmacophore, is utilized as the highly biocompatible ligand, and the Zn (II) coordinative quinoline‐based ligand also provides the robust self‐fluorescence character. And the ROS‐responsive thioketal spacer is introduced to trigger the siRNA controlled release into cytoplasm. Consequently, by the synergistic effects between Zn‐QS and LMW PEI on improving several crucial transfection‐efficiency‐related steps, the representative Zn‐PQ4 exhibits very high transfection efficiency of 1.8 and 2.5‐folds commercial Lipo2k and PEI25k in stem cell rADSC, respectively, >90% of transfection rates in a variety of conventional cell lines (3T3, HK‐2, HepG2, 293T, HeLa, PANC‐1), and 98.4% and 99.9% EGFP knockdown rates in 293T and HepG2 cells, respectively. Furthermore, Zn‐PQ4/siRNA polyplexes can circumvent various obstacles existing in systemic application to accumulate in heart, liver, and kidney and greatly silence the DNA expression in vivo. This work demonstrates the promising application prospects of the resulting efficient siRNA carriers in siRNA‐mediated gene therapy and fluorescence‐guided research.

Development of novel aspartic acid-based calcium bio-MOF designed for the management of severe bleeding

The synthesis of amino acid-based MOF using calcium as metal ion and l-aspartic acid biocompatible ligand for management of severe bleeding.

Biocompatible ligands modulate nanozyme activity of CeO2nanoparticles

The modification of CeO2nanoparticles with common biocompatible ligands allows regulating nanozyme property of nanoceria, namely SOD-like property, and its antioxidant activity.

Molecular Level Sucrose Quantification: A Critical Review.

Sucrose is a primary metabolite in plants, a source of energy, a source of carbon atoms for growth and development, and a regulator of biochemical processes. Most of the traditional analytical chemistry methods for sucrose quantification in plants require sample treatment (with consequent tissue destruction) and complex facilities, that do not allow real-time sucrose quantification at ultra-low concentrations (nM to pM range) under in vivo conditions, limiting our understanding of sucrose roles in plant physiology across different plant tissues and cellular compartments. Some of the above-mentioned problems may be circumvented with the use of bio-compatible ligands for molecular recognition of sucrose. Nevertheless, problems such as the signal-noise ratio, stability, and selectivity are some of the main challenges limiting the use of molecular recognition methods for the in vivo quantification of sucrose. In this review, we provide a critical analysis of the existing analytical chemistry tools, biosensors, and synthetic ligands, for sucrose quantification and discuss the most promising paths to improve upon its limits of detection. Our goal is to highlight the criteria design need for real-time, in vivo, highly sensitive and selective sucrose sensing capabilities to enable further our understanding of living organisms, the development of new plant breeding strategies for increased crop productivity and sustainability, and ultimately to contribute to the overarching need for food security.

Synthesis and characterization of thermoplastic poly(piperazine succinate) metallopolymers coordinated to ruthenium(III) or iron(III)

AbstractMetal‐containing polymers represent an ever‐expanding frontier of material science. Of the numerous biocompatible ligands used to create a metallopolymer, piperazine‐containing polymers are still in their early development, even though piperazine is a common functional group in drug design and bioengineering scaffolding elements. We report the first synthesis and characterization (with NMR, IR, GPC, UV–vis spectroscopy, and thermal analysis) of two thermoplastic poly(alkyl piperazine succinate) diols with either propyl or hexyl alkane chains bridging the piperazines. These polyester diols were then chain extended with hexamethylene diisocyanate to create highly amorphous polyester urethane thermoplastic polymers. Ru(III) or Fe(III) was then successfully coordinated with these polymers, with approximately 30% of the bulk metallopolymer product becoming 250x the molecular weight of the non‐metal containing polymers. However, coordination of Fe(III), and to a lesser extent Ru(III), to these polypiperazines accelerated the hydrolysis of the polyester linkage in water over 15 days. Thus, these novel polymers are highly biodegradable with Fe(III) metallopolymers hydrolyzing faster than Ru(III) metallopolymers and poly(propyl piperazine succinate) polymers hydrolyzing faster than poly(hexyl piperazine succinate) polymers.

Nanoscale Coordination Polymer Based on Bacterial Derivatives for Enhanced Radiotherapy in Neuroblastoma

Neuroblastoma (NB) is one of the most common extracranial malignancies in children, accounting for 7–8% of childhood malignancies. As one of the main treatments for NB, radiotherapy is limited by various factors in clinics, such as the hypoxia microenvironment in tumor and serious side effects. Herein, we synthesized a kind of nanoscale coordination polymer denoted as Hf@DAP nanoparticles composed of hafnium ion (Hf[Formula: see text] and 2,6-diaminopimelic acid (DAP), one of bacterial derivatives. From the image of transmission electron microscope (TEM), nanoparticles had uniform dispersion. Furthermore, the hydrodynamic diameter measured by dynamic light scattering method was about 190 nm. In this structure, the Hf[Formula: see text] can enhance radiotherapy by effectively enhancing the function of X-ray, and the DAP was a biocompatible ligand for fabricating the nanoscale coordination nanoparticles. Furthermore, Hf@DAP nanoparticles were stable in various mediums and exhibited favorable biocompatibility in various cell lines in vitro. Cell viabilities were tested by cell counting kit (CCK-8) in vitro. There was no obvious cytotoxicity to normal cells, including NIH3T3, RAW264.7, and HUVECs, after incubation with Hf@DAP nanoparticles, indicating biocompatibilities of Hf@DAP nanoparticles. Additionally, a significantly enhanced radiotherapy effect was observed in the N2a cells, a kind of NB cell line, pretreated with Hf@DAP nanoparticles in vitro. The in vivo tumor growth was obviously inhibited in the mice with the combined therapy of Hf@DAP nanoparticles and X-ray, compared with PBS group, Hf@DAP group, and X-ray group. Furthermore, the survival time of the mice in the combined group was significantly prolonged, compared with PBS group. In addition, tissues structures of main organs, such as the lung, liver, spleen, and kidney in these mice, were ordered without the influence of Hf@DAP nanoparticles. Thus, this work proposed a potential radio-sensitizer for further clinical radiotherapy with limited side effects and high efficiency.

Nano-Sized Antioxidative Trimetallic Complex Based on Maillard Reaction Improves the Mineral Nutrients of Apple (Malus domestica Borkh.).

The metallic complex is widely used in agricultural applications. Due to the oxidation of the metal and environmental unfriendliness of ligand, maintaining an efficient mineral supply for plants without causing environmental damage is difficult. Herein, an antioxidative trimetallic complex with high stability was synthesized by interacting Ca2+, Fe2+, and Zn2+ with the biocompatible ligands from the Maillard reaction. The composite structure elucidation was carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR). Thermal stability was measured by thermogravimetric (TG). Antioxidative activities were evaluated by ferric reducing antioxidant power and radical scavenging activity assays. The three metals were successfully fabricated on the Maillard reaction products (MRPs) with contents of Ca (9.01%), Fe (8.25%), and Zn (9.67%). Microscopy images revealed that the three metals were uniformly distributed on the MRPs with partial aggregation of <30 nm. FTIR and XPS results revealed that the metals were interacted with MRPs by metal–O and metal–N bonds. TG and antioxidative activity assays showed that the trimetallic complex meets the requirements of thermodynamics and oxidation resistance of horticultural applications. Additionally, the results of the exogenous spraying experiment showed that the trimetallic complex significantly increased the mineral contents of the “Fuji” apple. By treatment with the complex, the concentrations of Ca, Fe, and Zn were increased by 85.4, 532.5, and 931.1% in the leaf; 16.0, 225.2, and 468.6% in the peel; and 117.6, 217.9, and 19.5% in the flesh, respectively. The MRP-based complexes offered a higher growth rate of the mineral content in apples than ones based on sugars or amino acids. The results of the spraying experiment carried out in 2 years show that the method has high reproducibility. This study thus promotes the development of green metallic complexes and expands the scope of agrochemical strategy.

Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv.

Biological metal-organic frameworks (BioMOFs) are hybrid compounds in which metal nodes are linked to biocompatible organic ligands and have potential for medical application. Herein, we developed a novel BioMOF modified with an anti-VEGFR1 scFv antibody (D16F7 scFv). Our BioMOF is co-loaded with a combination of an anticancer compound and a lipid-lowering drug to simultaneously suppress the proliferation, growth rate and metastases of cancer cells in cell culture model system. In particular, Prodigiosin (PG) and Simvastatin (SIM) were co-loaded into the newly synthesized Ca-Gly BioMOF nanoparticles coated with maltose and functionalized with a recombinant maltose binding protein-scFv fragment of anti-VEGFR1 (Ca-Gly-Maltose-D16F7). The nanoformulation, termed PG + SIM-NP-D16F7, has been shown to have strong active targeting behavior towards VEGFR1-overexpresing cancer cells. Moreover, the co-delivery of PG and SIM not only effectively inhibits the proliferation of cancer cells, but also prevents their invasion and metastasis. The PG + SIM-NP-D16F7 nanocarrier exhibited stronger cytotoxic and anti-metastatic effects compared to mono-treatment of free drugs and drug-loaded nanoparticles. Smart co-delivery of PG and SIM on BioMOF nanoparticles had synergistic effects on growth inhibition and prevented cancer cell metastasis. The present nanoplatform can be introduced as a promising tool for chemotherapy compared with mono-treatment and/or non-targeted formulations.

Paramagnetic ultrasmall Ho2O3 and Tm2O3 nanoparticles: characterization of r2 values and in vivo T2 MR images at a 3.0 T MR field

Paramagnetic ultrasmall Ho2O3 and Tm2O3 nanoparticles grafted with various hydrophilic and biocompatible ligands as a new class of efficient T2 MRI contrast agents were investigated in this study.

Flow Characteristics of the Conjugate of Anti-CD3 Monoclonal Antibodies and Magnetic Nanoparticle in PBS and Blood Vessels.

Previously, anti-CD3 antibodies delivered intravenously have been known for their negative side effects. The experimental conditions for optimal liquid production are derived from the Fc-directed conjugation of anti-CD3 foralumab antibodies and magnetic nanoparticles (Ab-MNPs). The anti-CD3 antibodies are prepared for conjugation with MNPs using SiteClick antibody labelling kits. The successful conjugation of the Ab-MNPs is confirmed using a transmission electron microscopy (TEM) image and an energy dispersive spectroscopy (EDS) analysis. The average values ​​of the moving speed of MNPs and Ab-MNPs in phosphate buffer saline (PBS) were+3.16 pix/frame and +6.70 pix/frame in the x-axis, respectively. This implies that MNPs with CD3 antibodies attached to the surface through biocompatible ligand functional groups has better fluidity in PBS. Afterwards, a non-clinical animal testing for the flow characteristics of Ab-MNPs inside a blood vessel is carried out to observe the effects of Ab-MNP delivery through intravenous injection.

Novel Perspectives towards RNA-Based Nano-Theranostic Approaches for Cancer Management.

In the fight against cancer, early diagnosis is critical for effective treatment. Traditional cancer diagnostic technologies, on the other hand, have limitations that make early detection difficult. Therefore, multi-functionalized nanoparticles (NPs) and nano-biosensors have revolutionized the era of cancer diagnosis and treatment for targeted action via attaching specified and biocompatible ligands to target the tissues, which are highly over-expressed in certain types of cancers. Advancements in multi-functionalized NPs can be achieved via modifying molecular genetics to develop personalized and targeted treatments based on RNA interference. Modification in RNA therapies utilized small RNA subunits in the form of small interfering RNAs (siRNA) for overexpressing the specific genes of, most commonly, breast, colon, gastric, cervical, and hepatocellular cancer. RNA-conjugated nanomaterials appear to be the gold standard for preventing various malignant tumors through focused diagnosis and delivering to a specific tissue, resulting in cancer cells going into programmed death. The latest advances in RNA nanotechnology applications for cancer diagnosis and treatment are summarized in this review.

Luminescent – Superparamagnetic iron oxide nanoparticles functionalized with biomolecules and lanthanides ions. Potential platforms for theranostic applications

This investigation describes the synthesis, characterization, and in vitro cytotoxic evaluation of luminescent-superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with biomolecules and Eu3+ and Tb3+ complexes. They emerge as strong candidates for a large number of biomedical applications, such as drug delivery for bioapplications in therapy and diagnosis (theranostic). Aiming these applications, magnetite nanoparticles (Fe3O4) functionalized with biocompatible ligands, Chitosan (CS) and Glutathione (GSH) and Eu3+ and Tb3+ β-Diketonates complexes were synthesized by a one-step procedure and characterized by different experimental techniques. Regarding bioapplication, their cytotoxicity using the cell viability assay of the blood mononuclear cell fraction were performed. The results show that the cytotoxicity depends on the concentration, nature of ligands and complexes. The SPIONs are luminescent with emission in the visible region under ultraviolet excitation and stable in nanoscale in aqueous medium. They are good candidates as nano-luminescent carriers in biomedical applications.

Sustainable Synthesis of Cyclic Carbonates from Terminal Epoxides by a Highly Efficient CaI2/1,3-Bis[tris(hydroxymethyl)-methylamino]-propane Catalyst.

The nonstopping increment of atmospheric carbon dioxide (CO2) concentration keeps harming the environment and human life. The traditional concept of carbon capture and storage (CCS) is no longer sufficient and has already been corrected to carbon capture, utilization, and storage (CCUS). CCUS involves significant CO2 utilization, such as cyclic carbonate formation, for its cost effectiveness, less toxicity, and abundant C1 synthon in organic synthesis. However, the high thermodynamic and kinetic stability of CO2 limits its applications. Herein, we report a mild, efficient, and practical catalyst based on abundant, nontoxic CaI2 in conjunction with biocompatible ligand 1,3-bis[tris(hydroxymethyl)-methylamino]-propane (BTP) for CO2 fixation under atmospheric pressure with terminal epoxides to give the cyclic carbonates. The Job plot detected the 1:1 Ca2+/BTP binding stoichiometry. Furthermore, formation of a single crystal of the 1:1 Ca2+/BTP complex was confirmed by single-crystal X-ray crystallography. The bis(cyclic carbonate) products exhibit potentials for components in the non-isocyanate polyurethanes (NIPUs) process. Notably, this protocol shows attractive recyclability and reusability.