Coordination Polymers Derived from Non‐Steroidal Anti‐Inflammatory Drugs for Cell Imaging and Drug Delivery

A new series of Mn^II coordination polymers, namely, [{Mn(L)(H₂O)₂} ? 2 Nap]_∞ ( CP1 ), [{Mn(L)(Ibu)₂(H₂O)₂}]_∞ ( CP2 ), [{Mn(L)(Flr)₂(H₂O)₂}]_∞ ( CP3 ), [{Mn(L)(Ind)₂(H₂O)₂} ? H₂O]_∞ ( CP4 ), [{Mn₂(L)₂(μ‐Flu)₄(H₂O)} ? L]_∞ ( CP5 ), [{Mn₂(L)₂(μ‐Tol)₄(H₂O)₂}]_∞ ( CP6) and [{Mn₂(L)₂(μ‐Mef)₄(H₂O)₂}]_∞ ( CP7 ) (Nap=naproxen, Ibu=ibuprofen, Flr=flurbiprofen, Ind=indometacin, Flu=flufenamic acid, Tol=tolfenamic acid and Mef=mefenamic acid) derived from various non‐steroidal anti‐inflammatory drugs (NSAIDs) and the organic linker 1,2‐bis(4‐pyridyl)ethylene (L) have been synthesized with the aim of being used for cell imaging and drug delivery. Single‐crystal X‐ray diffraction (SXRD) studies revealed that the NSAID molecules were part of the coordination polymeric network either through coordination to the metal center (in the majority of the cases) or through hydrogen bonding. Remarkably, all the Mn^II coordination polymers were found to be soluble in DMSO, thereby making them particularly suitable for the desired biological applications. Two of the coordination polymers (namely, CP1 and CP3 ) reported herein, were found to be photoluminescent both in the solid as well as in the solution state. Subsequent experiments (namely, MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide), and PGE₂ (prostaglandin E₂) assays) established their biocompatibility and anti‐inflammatory response. In vitro studies by using a macrophage cell line (i.e., RAW 264.7) revealed that both CP1 and CP3 were excellent cell imaging agents. Finally, biodegradability studies under simulated physiological conditions in phosphate‐buffered saline (PBS) at pH 7.6 showed that slow and sustained release of the corresponding NSAID was indeed possible from both CP1 and CP3 .     

纳米金属有机框架材料在药物递送领域的应用

金属有机框架材料(Metal-Organic Frameworks, MOFs)是一类由金属离子及有机配体自组装而成的多孔材料,具有孔隙率高、比表面积大和结构多样化等独特优点,广泛应用于气体储存、物质分离和催化等领域。纳米尺寸金属有机框架材料(Nanoscale Metal-Organic Frameworks, NMOFs)既保持了传统MOFs的规整性,也具有纳米颗粒的特殊性质,在生物医药领域中是绝佳的药物载体。相比于传统纳米药物载体,NMOFs与药物的结合方式丰富,展现了多种药物装载模式,可以满足不同药物的制备需求,也可引入不同功能分子优化性能。最近,有越来越多的研究报道了多功能化NMOFs应用于药物递送领域,并实现刺激响应性的可控释放。本文将着重对NMOFs材料作为药物载体负载抗癌药物、光敏剂和核酸的应用进展进行综述。     

Fluorescent Protein Capped Mesoporous Nanoparticles for Intracellular Drug Delivery and Imaging

A multifunctional system for intracellular drug delivery and simultaneous fluorescent imaging was constructed by using histidine‐tagged, cyan fluorescent protein (CFP)‐capped magnetic mesoporous silica nanoparticles (MMSNs). This protein‐capped multifunctional nanostructure is highly biocompatible and does not affect cell viability or proliferation. The CFP acts not only as a capping agent, but also as a fluorescent imaging agent. The nanoassembly was activated by histidine‐based replacement, leading to release of drug molecules encapsulated in the nanopores into the bulk solution. The fluorescent imaging functionality would allow noninvasive tracking of the nanoparticles in the body. By combining the drug delivery with cell‐imaging capability, these nanoparticles may provide valuable multifunctional nanoplatforms for biomedical applications.     

One‐Step Synthesis of Small‐Sized and Water‐Soluble NaREF4 Upconversion Nanoparticles for In Vitro Cell Imaging and Drug Delivery

Small (2–28 nm) NaREF₄ (rare earth (RE)=Nd–Lu, Y) nanoparticles (NPs) were prepared by an oil/water two‐phase approach. Meanwhile, hydrophilic NPs can be obtained through a successful phase‐transition process by introducing the amphiphilic surfactant sodium dodecylsulfate (SDS) into the same reaction system. Hollow‐structured NaREF₄ (RE=Y, Yb, Lu) NPs can be fabricated in situ by electron‐beam lithography on solid NPs. The MTT assay indicates that these hydrophilic NPs with hollow structures exhibit good biocompatibility. The as‐prepared hollow‐structured NPs can be used as anti‐cancer drug carriers for drug storage/release investigations. Doxorubicin hydrochloride (DOX) was taken as model drug. The release of DOX from hollow α‐NaLuF₄:20 % Yb³⁺, 2 % Er³⁺ exhibits a pH‐sensitive release patterns. Confocal microscopy observations indicate that the NPs can be taken up by HeLa cells and show obvious anti‐cancer efficacy. Furthermore, α‐NaLuF₄:20 % Yb³⁺, 2 % Er³⁺ NPs show bright‐red emission under IR excitation, making both the excitation and emission light fall within the “optical window” of biological tissues. The application of α‐NaLuF₄:20 % Yb³⁺, 2 % Er³⁺ in the luminescence imaging of cells was also investigated, which shows a bright‐red emission without background noise.     

pH-Responsive Drug Delivery and Imaging Study of Hybrid Mesoporous Silica Nanoparticles

A system of pH-responsive and imaging nanocarriers was developed using mesoporous silica nanoparticles (MSNs), in which gadolinium (Gd) was doped through in situ doping (Gd₂O₃@MSN). Sodium alginate (SA) was attached to the surfaces of the amino groups of MSNs (NH₂-Gd₂O₃@MSN) through the electrostatic adsorption between the amino groups and the carboxyl groups with the formation of hybrid SA-Gd₂O₃@MSN nanoparticles (NPs). The SA-coated NPs were spherical or near-spherical in shape with an average size of nearly 83.2 ± 8.7 nm. The in vitro drug release experiments of a model rhodamine B (RhB) cargo were performed at different pH values. The result confirmed the pH-responsiveness of the nanocarriers. The results of the cytotoxicity studies indicated that the SA-Gd₂O₃@MSN NPs were not cytotoxic by themselves. The results of the in vivo safety evaluation and the hemolysis assay confirmed that the system is highly biocompatible. It is noteworthy that the T1 contrast of the system was significantly enhanced by the Gd, as indicated by the result of the MR imaging. This study confirms that the synthesized hybrid nanosystem is promising for pH-responsive drug delivery and MR imaging for cancer diagnosis and treatment.     

Conjugated Polymer Nanoparticles with Appended Photo‐Responsive Units for Controlled Drug Delivery,Release, and Imaging

Carriers that can afford tunable physical and structural changes are envisioned to address critical issues in controlled drug delivery applications. Herein, photo‐responsive conjugated polymer nanoparticles (CPNs) functionalized with donor–acceptor Stenhouse adduct (DASA) and folic acid units for controlled drug delivery and imaging are reported. Upon visible‐light (λ=550 nm) irradiation, CPNs simultaneously undergo structure, color, and polarity changes that release encapsulated drugs into the cells. The backbone of CPNs favors FRET to DASA units boosting their fluorescence. Notably, drug‐loaded CPNs exhibit excellent biocompatibility in the dark, indicating perfect control of the light trigger over drug release. Delivery of both hydrophilic and hydrophobic drugs with good loading efficiency was demonstrated. This strategy enables remotely controlled drug delivery with visible‐light irradiation, which sets an example for designing delivery vehicles for non‐invasive therapeutics.     

Recent Advances in Aggregation-Induced Emission Active Materials for Sensing of Biologically Important Molecules and Drug Delivery System

The emergence and development of aggregation induced emission (AIE) have attracted worldwide attention due to its unique photophysical phenomenon and for removing the obstacle of aggregation-caused quenching (ACQ) which is the most detrimental process thereby making AIE an important and promising aspect in various fields of fluorescent material, sensing, bioimaging, optoelectronics, drug delivery system, and theranostics. In this review, we have discussed insights and explored recent advances that are being made in AIE active materials and their application in sensing, biological cell imaging, and drug delivery systems, and, furthermore, we explored AIE active fluorescent material as a building block in supramolecular chemistry. Herein, we focus on various AIE active molecules such as tetraphenylethylene, AIE-active polymer, quantum dots, AIE active metal-organic framework and triphenylamine, not only in terms of their synthetic routes but also we outline their applications. Finally, we summarize our view of the construction and application of AIE-active molecules, which thus inspiring young researchers to explore new ideas, innovations, and develop the field of supramolecular chemistry in years to come.     

DNA Nanoflowers for Multiplexed Cellular Imaging and Traceable Targeted Drug Delivery

We present a facile approach to make aptamer‐conjugated FRET (fluorescent resonance energy transfer) nanoflowers (NFs) through rolling circle replication for multiplexed cellular imaging and traceable targeted drug delivery. The NFs can exhibit multi‐fluorescence emissions by a single‐wavelength excitation as a result of the DNA matrix covalently incorporated with three dye molecules able to perform FRET. Compared with the conventional DNA nanostructure assembly, NF assembly is independent of template sequences, avoiding the otherwise complicated design of DNA building blocks assembled into nanostructures by base‐pairing. The NFs were uniform and exhibited high fluorescence intensity and excellent photostability. Combined with the ability of traceable targeted drug delivery, these colorful DNA NFs provide a novel system for applications in multiplex fluorescent cellular imaging, effective screening of drugs, and therapeutic protocol development.     

Enzyme‐Responsive Multifunctional Magnetic Nanoparticles for Tumor Intracellular Drug Delivery and Imaging

Enzyme‐responsive, hybrid, magnetic silica nanoparticles have been employed for multifunctional applications in selective drug delivery and intracellular tumor imaging. In this study, doxorubicin (Dox)‐conjugated, enzyme‐cleavable peptide precursors were covalently tethered onto the surface of uniform silica‐coated magnetic nanoparticles through click chemistry. This enzyme‐responsive nanoparticle conjugate demonstrated highly efficient Dox release upon specific enzyme interactions in vitro. It also exhibits multiple functions in selective tumor intracellular drug delivery and imaging in the tumor cells with high cathepsin B expression, whereas it exhibited lower cytotoxicity towards other cells without enzyme expression.     

Metal-Organic Frameworks Nanocarriers for Functional Nucleic Acid Delivery in Biomedical Applications

Metal−organic frameworks (MOFs), a distinctive funtionalmaterials which is constructed by various metal ions and organic molecules, have gradually attracted researchers′ attention from they were founded. In the last decade, MOFs emerge as a biomedical material with potential applications due to their unique properties. However, the MOFs performed as nanocarriers for functional nucleic acid delivery in biomedical applications rarely summarized. In this review, we introduce recent developments of MOFs for nucleic acid delivery in various biologically relevant applications, with special emphasis on cancer therapy (including siRNA, ASO, DNAzyme, miRNA and CpG oligodeoxynucleotides), bioimaging, biosensors and separation of biomolecules. We expect the accomplishment of this review could benefit certain researchers in biomedical field to develop novel sophisticated nanocarriers for functional nucleic acid delivery based on the promising material of MOFs.     

纳米金属有机骨架材料及其载药应用

金属有机骨架材料(MOFs)是指由含氮、氧等多齿有机配体与金属离子通过自组装形成的配位聚合物。由于金属有机骨架材料的大比表面积和高孔隙率等优点使其在药物负载领域有广泛应用。近年来,纳米金属有机骨架材料(NMOFs)因既具有MOFs的特点,又具有纳米材料独特的理化性能,使其兼具药物负载量高、目标靶向性好、表面易改性和生物相容性优良等特点,已成为一种优异的纳米级载药系统。本文介绍了NMOFs的常用制备方法,主要包括溶剂热法、反相微乳液法与超声波法,并对其优缺点进行了讨论;详细阐述了载药NMOFs的特性及其不同类型对于各类药物的负载能力;指出今后其主要的研究方向是改善生物相容性、实现更有效的表面功能化、扩展生物NMOFs及其负载药物的种类,使其应用到更多疾病的治疗上。     

Microwave-Assisted Synthesis,Characterization and Modeling of CPO-27-Mg Metal-Organic Framework for Drug Delivery

The coordination polymer CPO-27-Mg was rapidly synthesized under microwave irradiation. This material exhibits a sufficiently high drug loading towards aspirin (~8% wt.) and paracetamol (~14% wt.). The binding of these two molecules with the inner surface of the metal-organic framework was studied employing the Gaussian and Plane Wave approach of the Density Functional Theory. The structure of CPO-27-Mg persists after the adsorption of aspirin or paracetamol and their desorption energies, being quite high, decrease under solvent conditions.     

Nanoscale Biodegradable Organic–Inorganic Hybrids for Efficient Cell Penetration and Drug Delivery

We report a comprehensive study on novel, highly efficient, and biodegradable hybrid molecular transporters. To this end, we designed a series of cell‐penetrating, cube‐octameric silsesquioxanes (COSS), and investigated cellular uptake by confocal microscopy and flow cytometry. A COSS with dense spatial arrangement of guanidinium groups displayed fast uptake kinetics and cell permeation at nanomolar concentrations in living HeLa cells. Efficient uptake was also observed in bacteria, yeasts, and archaea. The COSS‐based carrier was significantly more potent than cell‐penetrating peptides (CPPs) and displayed low toxicity. It efficiently delivered a covalently attached cytotoxic drug, doxorubicin, to living tumor cells. As the uptake of fluorescently labeled carrier remained in the presence of serum, the system could be considered particularly attractive for the in vivo delivery of therapeutics.     

Hybrid Polymeric Nanomaterials for siRNA Delivery and Imaging

A combined nanomaterials‐based approach for simultaneous therapy and molecular imaging has powerful potential for efficient treatment and monitoring the prognosis of incurable diseases such as malignant tumors or degenerative diseases. Recent developments of hybrid polymeric nanomaterials for siRNA delivery and imaging are highlighted. A particular focus is on various conjugation and formulation strategies of how to incorporate siRNA and imaging agents onto the surface of functionally active polymer‐coated inorganic nanomaterials such as iron oxide, gold, and quantum‐dot nanoparticles for theranostic applications. These multifunctional nanocarriers may allow real‐time tracking of siRNA as well as visualization of its therapeutic effects in vitro and in vivo.

     

Multidrug‐Containing,Salt‐Based,Injectable Supramolecular Gels for Self‐Delivery,Cell Imaging and Other Materials Applications

Both molecular and crystal‐engineering approaches were exploited to synthesize a new class of multidrug‐containing supramolecular gelators. A well‐known nonsteroidal anti‐inflammatory drug, namely, indomethacin, was conjugated with six different l ‐amino acids to generate the corresponding peptides having free carboxylic acid functionality, which reacted further with an antiviral drug, namely, amantadine, a primary amine, in 1:1 ratio to yield six primary ammonium monocarboxylate salts. Half of the synthesized salts showed gelation ability that included hydrogelation, organogelation and ambidextrous gelation. The gels were characterized by table‐top and dynamic rheology and different microscopic techniques. Further insights into the gelation mechanism were obtained by temperature‐dependent ¹H NMR spectroscopy, FTIR spectroscopy, photoluminescence and dynamic light scattering. Single‐crystal X‐ray diffraction studies on two gelator salts revealed the presence of 2D hydrogen‐bonded networks. One such ambidextrous gelator (capable of gelling both pure water and methyl salicylate, which are important solvents for biological applications) was promising in both mechanical (rheoreversible and injectable) and biological (self‐delivery) applications for future multidrug‐containing injectable delivery vehicles.     

功能化金属-有机框架材料在肿瘤治疗中的研究进展

恶性肿瘤由于其易转移、复发等特点,已经严重危害到人类的生命健康.近年来,研究人员设计了大量纳米药物载体,将抗肿瘤药物安全有效地运载到肿瘤,有效地提高了药效并降低了毒副作用.金属有机框架材料（metal-organic frameworks,MOFs）是一类有序、多孔的晶态材料,具有比表面积大、结构可设计性强、易生物降解等独特优势,已经被广泛应用于气体吸附与分离、催化、药物传递、生物大分子固载以及肿瘤治疗等方面.目前,基于MOFs的生物医用研究主要集中在MOF材料的可控合成,表面修饰,基于MOF独特理化性质发展的多模式成像技术以及肿瘤靶向的药物运载技术等几个方面.主要介绍了基于MOFs构建的生物功能化材料在肿瘤治疗中的应用,并对其在生物医学领域的应用进行了展望.     

金属有机框架抗菌材料的研究进展

细菌耐药问题已经成为了中国乃至全球的重大公共健康威胁,设计合成新型抗菌材料以减少抗生素依赖成为当前化学化工、材料和生物医学领域中的重要研究课题.金属有机框架(Metal-organic frameworks, MOFs)材料是由有机配体和金属离子或团簇通过配位键自组装形成的多孔晶态材料,在气体吸附与分离、传感和催化等领域都扮演着重要角色.为了寻求更好应对细菌威胁的方式方法,国内外研究者们纷纷构建出不同结构的MOFs材料,并将其应用于抗菌领域.本综述从细菌耐药性的产生和MOFs抗菌机理等方面出发,分类概述了不同金属中心和配体MOFs材料、MOFs包覆金属纳米粒子材料和药物缓释MOFs材料等在抗菌、促进伤口愈合等方面的应用,归纳概括了MOFs材料在抗菌领域应用中仍需解决的科学问题,并对该领域的发展趋势进行了展望.     

Nanomaterials for Ocular Drug Delivery

Efficient drug delivery to the eye remains a challenging task for pharmaceutical scientists. Due to the various anatomical barriers and the clearance mechanisms prevailing in the eye, conventional drug delivery systems, such as eye drop solutions, suffer from low bioavailability. More invasive methods, such as intravitreal injections and implants, cause adverse effects in the eye. Recently, an increasing number of scientists have turned to nanomaterial‐based drug delivery systems to address the challenges faced by conventional methods. This paper highlights recent applications of various nanomaterials, such as polymeric micelles, hydrogels, liposomes, niosomes, dendrimers, and cyclodextrins as ocular drug delivery systems to enhance the bioavailability of ocular therapeutic agents.

     

Genetically Encoded Activators of Small Molecules for Imaging and Drug Delivery

Chemical biologists have developed many tools based on genetically encoded macromolecules and small, synthetic compounds. The two different approaches are extremely useful, but they have inherent limitations. In this Minireview, we highlight examples of strategies that combine both concepts to tackle challenging problems in chemical biology. We discuss applications in imaging, with a focus on super‐resolved techniques, and in probe and drug delivery. We propose future directions in this field, hoping to inspire chemical biologists to develop new combinations of synthetic and genetically encoded probes.