Recent Biomedical Applications of Functional Materials Based on Polyhedral Oligomeric Silsesquioxane (POSS).

Polyhedral oligomeric silsesquioxane (POSS) is a 3D, cage-like nanoparticle with an inorganic Si-O-Si core and eight tunable corner functional groups. Its well-defined structure grants it distinctive physical, chemical, and biological properties and has been widely used for preparing high-performance materials. Recently, click chemistry has enabled the synthesis of various functional POSS-based materials for diverse biomedical applications. This article reviews the recent applications of POSS-based materials in the biomedical field, including cancer treatment, tissue engineering, antibacterial use, and biomedical imaging. Representative examples are discussed in detail. Among the various POSS-based applications, cancer treatment and tissue engineering are the most important. Finally, this review presents the current limitations of POSS-based materials and provides guidance for future research.

Biosensor for ATP detection via aptamer-modified PDA@POSS nanoparticles synthesized in a microfluidic reactor.

This study introduces aptamer-functionalized polyhedral oligomeric silsesquioxane (POSS) nanoparticles for adenosine triphosphate (ATP) detection where the POSS nanoparticles were synthesized in a one-step, continuous flow microfluidic reactor utilizing thermal polymerization. A microemulsion containing POSS monomers was generated in the microfluidic reactor which was designed to prevent clogging by using a continuous oil flow around the emulsion during thermal polymerization. Surfaces of POSS nanoparticles were biomimetically modified by polydopamine. The aptamer sequence for ATP was successfully attached to POSS nanoparticles. The aptamer-modified POSS nanoparticles were tested for affinity-based biosensor applications using ATP as a model molecule. The nanoparticles were able to capture ATP molecules successfully with an affinity constant of 46.5 [Formula: see text]M. Based on this result, it was shown, for the first time, that microfluidic synthesis of POSS nanoparticles can be utilized in designing aptamer-functionalized nanosystems for biosensor applications. The integration of POSS in biosensing technologies not only exemplifies the versatility and efficacy of these nanoparticles but also marks a significant contribution to the field of biorecognition and sample preparation.

Polyhedral Oligomeric Silsesquioxane-Based Nanoparticles for Efficient Chemotherapy of Glioblastoma.

Glioblastoma (GBM) is the most common lethal brain tumor with dismal treatment outcomes and poor response to chemotherapy. As the regulatory center of cytogenetics and metabolism, most tumor chemotherapeutic molecules exert therapeutic effects in the nucleus. Nanodrugs showing the nuclear aggregation effect are expected to eliminate and fundamentally suppress tumor cells. In this study, a nanodrug delivery system based on polyhedral oligomeric silsesquioxane (POSS) is introduced to deliver drugs into the nuclei of GBM cells, effectively enhancing the therapeutic efficacy of chemotherapy. The nanoparticles are modified with folic acid and iRGD peptides molecules to improve their tumor cell targeting and uptake via receptor-mediated endocytosis. Nuclear aggregation allows for the direct delivery of chemotherapeutic drug temozolomide (TMZ) to the tumor cell nuclei, resulting in more significant DNA damage and inhibition of tumor cell proliferation. Herein, TMZ-loaded POSS nanoparticles can significantly improve the survival of GBM-bearing mice. Therefore, the modified POSS nanoparticles may serve as a promising drug-loaded delivery platform to improve chemotherapy outcomes in GBM patients.

Regioisomeric Giant Triblock Molecules: Role of the Linker.

In this study, polyhedral oligomeric silsesquioxane (POSS) based giant triblock molecules with precisely defined regio-configuration are modularly prepared through highly efficient coupling reactions. The length of the linker connecting neighboring nanoparticles is elaborately designed to regulate the geometric constraints. The triblock molecules adopt a folded packing during phase separation, and the regio-configuration imparts direct influence on the self-assembly behaviors. The ortho-isomers form periodic structures with a larger domain size, larger interfacial curvature, and enhanced phase stability. The regio-effect is closely related to the length and symmetry of the linker. As the linker extends, the neighboring particles gradually decouple, and the regio-effect diminishes. The symmetry of the linker shows an even more profound impact. This work quantitatively scrutinized the role of the linker, opening an avenue for engineering the assembled structures with molecular precision.

Efficient Adsorption and Extraction of Glutathione S-Transferases with Glutathione-Functionalized Graphene Oxide-Polyhedral Oligomeric Silsesquioxane Composite.

Glutathione S-transferases (GSTs) are important type-II detoxification enzymes that protect DNA and proteins from damage and are often used as protein tags for the expression of fusion proteins. In the present work, octa-aminopropyl caged polyhedral oligomeric silsesquioxane (OA-POSS) was prepared via acid-catalyzed hydrolysis of 3-aminopropyltriethoxysilane and polymerized on the surface of graphene oxide (GO) through an amidation reaction. Glutathione (GSH) was then modified to GO-POSS through a Michael addition reaction to obtain a GSH-functionalized GO-POSS composite (GPG). The structure and characteristics of the as-prepared GPG composite were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermogravity analysis, and surface charge analysis. The specific binding interactions between glutathione and GST gave GPG favorable adsorption selectivity towards GST, and other proteins did not affect GST adsorption. The adsorption behavior of GST on the GPG composite conformed to the Langmuir isotherm model, and the adsorption capacity of GST was high up to 364.94 mg g-1 under optimal conditions. The GPG-based solid-phase adsorption process was applied to the extraction of GST from a crude enzyme solution of pig liver, and high-purity GST was obtained via SDS-PAGE identification.

POSS-based fluorescence sensor for rapid analysis of ß-carotene in health products.

In recent years, fluorescent organic-inorganic hybrid nanomaterials have received much interest as potential fluorescent sensor materials. In this study, fluorescent organic-inorganic hybrid nanomaterials (POSS@ANT) were created using polyhedral oligomeric silsesquioxane as the precursor and 9,10-bromoanthracene as the monomer. The morphology and composition of POSS@ANT, as well as its pore characteristics and fluorescence properties were studied. POSS@ANT displayed steady fluorescence emission at an excitation wavelength of 374 nm. Next, a ß-carotene fluorescence sensor was developed using the capacity of ß-carotene to quench the fluorescence of POSS@ANT. The quenching process is linked to acceptor electron transfer and energy transfer, and the sensor has a high selectivity for ß-carotene. This ß-carotene fluorescence analysis method that we established has a linear range of 0.2-4.3 mg/L and a detection limit of 0.081 mg/L. Finally, it was used to quantify ß-carotene in health products, the recovery rate was 91.1-109.9%, the relative standard deviation (RSD) was 2.2-4.3%, and the results were comparable with the results of high-performance liquid chromatography. The approach is reliable and can be used to determine ß-carotene in health products.

Design of Fluorescent Hybrid Materials Based on POSS for Sensing Applications.

Polyhedral oligomeric silsesquioxane (POSS) has a nanoscale silicon core and eight organic functional groups on the surface, with sizes from 0.7 to 1.5 nm. The three-dimensional nanostructures of POSS can be used to build all types of hybrid materials with specific performance and controllable nanostructures. The applications of POSS-based fluorescent materials have spread across various fields. In particular, the employment of POSS-based fluorescent materials in sensing application can achieve high sensitivity, selectivity, and stability. As a result, POSS-based fluorescent materials are attracting increasing attention due to their fascinating vistas, including unique structural features, easy fabrication, and tunable optical properties by molecular design. Here, we summarize the current available POSS-based fluorescent materials from design to sensing applications. In the design section, we introduce synthetic strategies and structures of the functionalized POSS-based fluorescent materials, as well as photophysical properties. In the application section, the typical POSS-based fluorescent materials used for the detection of various target objects are summarized with selected examples to elaborate on their wide applications.

Constructing 3D Interconnected Si/SiOx /C Nanorings from Polyhedral Oligomeric Silsesquioxane.

Polyhedral oligomeric silsesquioxane (POSS) is a family of organic/inorganic hybrid materials with specific molecular symmetry, and shows great potential in the structural design of nanomaterials. Here, a "bottom-up" strategy is designed to fabricate 3D interconnected Si/SiOx /C nanorings (NRs) via AlCl3 -assisted aluminothermic reduction using dodecaphenyl cage silsesquioxane (T12 -Ph) as the building block. In this process, AlCl3 acts as both a liquid medium for reduction, and significantly as the catalyst to the cross-linking of phenyl groups in T12 -Ph. The obtained Si/SiOx /C NRs exhibits uniform diameter of ≈165 nm and well distribution of C and Si elements. The unique ring-like structure of Si/SiOx /C NRs makes it have great application potential in the field of lithium ion batteries. Notably, Si/SiOx /C NRs exhibits superior high-rate capacity and good cycle stability when used as anode for LIBs. More excitingly, Si/SiOx /C NRs can deliver a high reversible capacity of 517.9 mA h g-1 at ultra-low temperature of -70 °C, and the capacity retention as high as ≈50% of that at 25 °C. This work not only broadens structural design of carbon-based nanomaterials but also provides more possibilities for the application of POSS.

Mercapto-functionalized polyhedral oligomeric silsesquioxane as a soluble support for the synthesis of peptide thioesters.

The revival of peptide-based drugs has led to the increasing demand for the development of large-scale synthesis of these complex molecules. To meet this demand, the use of mercapto-functionalized polyhedral oligomeric silsesquioxane (POSS-SH) as a soluble support for the synthesis of a model pentapeptide POSS-thioester is reported. The synthetic process provided a total yield of 62% for the pentapeptide POSS-thioester and the 1H NMR spectra validated the high purity of the products. The successful synthesis of the pentapeptide POSS-thioester with high yield and purity provides a promising way to the scale-up chemical synthesis of peptide thioesters, peptides, peptide amides, cyclic peptides, and even proteins.

A turn-on-type fluorescence resonance energy transfer aptasensor for vibrio detection using aptamer-modified polyhedral oligomeric silsesquioxane-perovskite quantum dots/Ti3C2 MXenes composite probes.

A pair of composite probes based on aptamer modified polyhedral oligomeric silsesquioxane-perovskite quantum dots (POSS-PQDs-Apt) as signal probe and titanium carbide (Ti3C2) MXenes as quencher were prepared for the first time. They were employed to fabricate one turn-on-type aptasensor relying on fluorescence resonance energy transfer (FRET) for Vibrio parahaemolyticus (VP) determination. The POSS-PQDs-Apt can be adsorbed on the MXenes nanosheets, and its fluorescence was quenched due to the FRET. After the composite probes were incubated with VP for 50 min, the POSS-PQDs-Apt binding with VP can be released from the surface of MXenes, and the signal recovered due to its higher affinity to the VP than MXenes. The fluorescence intensity from 519 nm emission of the system was measured at 480 nm excitation. Under In optimized conditions, the assay can determine VP in the concentration range 102 - 106 cfu/mL, and the detection limit (LOD) was 30 cfu/mL using fluorescence detection. The LOD is still 100 cfu/mL by naked eye detection which is proper for on-line monitoring VP in aquaculture water. This method was also used to detect VP in actual samples of seawater, the recovery of spiked samples was between 93% and 106%, and relative standard deviation (RSD) was between 2.7% and 6.7%. The result is consistent with the plate count. Therefore, this assay could provide a candidate platform for screening VP in aquaculture industry.

Synthesis of Silsesquioxanes with Substituted Triazole Ring Functionalities and Their Coordination Ability.

A synthesis of a series of mono-T8 and difunctionalized double-decker silsesquioxanes bearing substituted triazole ring(s) has been reported within this work. The catalytic protocol for their formation is based on the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) process. Diverse alkynes were in the scope of our interest-i.e., aryl, hetaryl, alkyl, silyl, or germyl-and the latter was shown to be the first example of terminal germane alkyne which is reactive in the applied process' conditions. From the pallet of 15 compounds, three of them with pyridine-triazole and thiophenyl-triazole moiety attached to T8 or DDSQ core were verified in terms of their coordinating properties towards selected transition metals, i.e., Pd(II), Pt(II), and Rh(I). The studies resulted in the formation of four SQs based coordination compounds that were obtained in high yields up to 93% and their thorough spectroscopic characterization is presented. To our knowledge, this is the first example of the DDSQ-based molecular complex possessing bidentate pyridine-triazole ligand binding two Pd(II) ions.

Use of Polyhedral Oligomeric Silsesquioxane (POSS) in Drug Delivery, Photodynamic Therapy and Bioimaging.

Polyhedral oligomeric silsesquioxanes (POSS) have attracted considerable attention in the design of novel organic-inorganic hybrid materials with high performance capabilities. Features such as their well-defined nanoscale structure, chemical tunability, and biocompatibility make POSS an ideal building block to fabricate hybrid materials for biomedical applications. This review highlights recent advances in the application of POSS-based hybrid materials, with particular emphasis on drug delivery, photodynamic therapy and bioimaging. The design and synthesis of POSS-based materials is described, along with the current methods for controlling their chemical functionalization for biomedical applications. We summarize the advantages of using POSS for several drug delivery applications. We also describe the current progress on using POSS-based materials to improve photodynamic therapies. The use of POSS for delivery of contrast agents or as a passivating agent for nanoprobes is also summarized. We envision that POSS-based hybrid materials have great potential for a variety of biomedical applications including drug delivery, photodynamic therapy and bioimaging.

Synthesis of a poly(sulfobetaine-co-polyhedral oligomeric silsesquioxane) hybrid monolith via an in-situ ring opening quaternization for use in hydrophilic interaction capillary liquid chromatography.

An in-situ approach is described for synthesis of poly(sulfobetaine-co-polyhedral oligomeric silsesquioxane) [poly(sulfobetaine-co-POSS)] that can be used in a hybrid monolithic column as a hydrophilic liquid chromatography (HILIC) stationary phase. Synthesis involves (a) radical polymerization of octa(propyl methacrylate)-polyhedral oligomeric silsesquioxane (MA-POSS) and organic monomers such as dimethylaminopropyl methacrylate or vinyl imidazole, and (b) in-situ ring-opening quaternization between 1,4-butane sultone and the organic monomers. The sulfobetaine groups are generated in-situ monolith. This obviates the need for synthesis of sulfobetaine monomer previously. The pore size and permeability of the material can be tuned by using a binary porogenic system (polyethyleneglycol 600 and acetonitrile) and via the composition of the polymerization mixture. The optimized hybrid monolith owns its merits to the presence of POSS and sulfobetaine groups with good mechanical stability, the lack of residual silanol groups, and adequate hydrophilicity. The column filled with the monoliths was evaluated as a stationary phase for HILIC. Several kinds of polar compounds (including nucleosides, bases, phenols, aromatic acids and amides) were separated by using mobile phases with high organic solvent fractions in capillary liquid chromatography. Graphical abstractAn in-situ approach is described for synthesis of poly(sulfobetaine-co-polyhedral oligomeric silsesquioxane) hybrid monolithic column for use in hydrophilic liquid chromatography. The optimized monolith owns good mechanical stability, the lack of residual silanol groups and adequate hydrophilicity. Baseline separation of several kinds of polar compounds is achieved on the column. MA-POSS: octa(propyl-methacrylate) polyhedral oligomeric silsesquioxane; DMAEMA: dimethylaminoethyl methacrylate; AIBN: azodiisobutyronitrile. Poly(DMABS-co-POSS): poly(N-(4-sulfobutyl)-N-methacryloxypropyl- N,N-dimethylammonium-betaine-co-polyhedral oligomeric silsesquioxane).

SAW Chemical Array Device Coated with Polymeric Sensing Materials for the Detection of Nerve Agents.

G nerve agents are colorless, odorless, and lethal chemical warfare agents (CWAs). The threat of CWAs, which cause critical damage to humans, continues to exist, e.g., in warfare or terrorist attacks. Therefore, it is important to be able to detect these agents rapidly and with a high degree of sensitivity. In this study, a surface acoustic wave (SAW) array device with three SAW sensors coated with different sensing materials and one uncoated sensor was tested to determine the most suitable material for the detection of nerve agents and related simulants. The three materials used were polyhedral oligomeric silsesquioxane (POSS), 1-benzyl-3-phenylthiourea (TU-1), and 1-ethyl-3-(4-fluorobenzyl) thiourea (TU-2). The SAW sensor coated with the POSS-based polymer showed the highest sensitivity and the fastest response time at concentrations below the median lethal concentration (LCt50) for tabun (GA) and sarin (GB). Also, it maintained good performance over the 180 days of exposure tests for dimethyl methylphosphonate (DMMP). A comparison of the sensitivities of analyte vapors also confirmed that the sensitivity for DMMP was similar to that for GB. Considering that DMMP is a simulant which physically and chemically resembles GB, the sensitivity to a real agent of the sensor coated with POSS could be predicted. Therefore, POSS, which has strong hydrogen bond acid properties and which showed similar reaction characteristics between the simulant and the nerve agent, can be considered a suitable material for nerve agent detection.

The Effect of POSS Type on the Shape Memory Properties of Epoxy-Based Nanocomposites.

Thermally activated shape memory polymers (SMPs) can memorize a temporary shape at low temperature and return to their permanent shape at higher temperature. These materials can be used for light and compact space deployment mechanisms. The control of transition temperature and thermomechanical properties of epoxy-based SMPs can be done using functionalized polyhedral oligomeric silsesquioxane (POSS) additives, which are also known to improve the durability to atomic oxygen in the space environment. In this study, the influence of varying amounts of two types of POSS added to epoxy-based SMPs on the shape memory effect (SME) were studied. The first type contained amine groups, whereas the second type contained epoxide groups. The curing conditions were defined using differential scanning calorimetry and glass transition temperature (Tg) measurements. Thermomechanical and SME properties were characterized using dynamic mechanical analysis. It was found that SMPs containing amine-based POSS show higher Tg, better shape fixity and faster recovery speed, while SMPs containing epoxide-based POSS have higher crosslinking density and show superior thermomechanical properties above Tg. This work demonstrates how the Tg and SME of SMPs can be controlled by the type and amount of POSS in an epoxy-based SMP nanocomposite for future space applications.

5 nm Ordered Structures Self-Assembled by C2 -Symmetric Hybrids with Polyhedral Oligomeric Silsesquioxane and Hexa-peri-Hexabenzocoronene.

Hybrids consisting of polyhedral oligomeric silsesquioxane (POSS) and hexa-peri-hexabenzocoronene (HBC) with a dumbbell topology and C2 symmetry were designed and synthesized. They self-assemble into 5 nm ordered structures. In particular, the increased steric effect with increasing POSS units stabilizes a square columnar phase (Colsqu ) which is important in nanotemplating. These hybrids containing discotic liquid crystal HBC and POSS units have an excellent etching contrast and present an approach to obtain 5 nm nanopatterns.

Polyhedral Oligomeric Silsesquioxane Hybrid Polymers: Well-Defined Architectural Design and Potential Functional Applications.

Polyhedral oligomeric silsesquioxane (POSS)-hybrid polymers have been successfully employed as functional inorganic-organic hybrid materials for various applications due to their well-determined structures. The past 6 years has witnessed growing interest in the rational design and synthetic approaches for POSS-hybrid polymers, driven by the adoption of controlled living radial polymerization and click chemistry. This review addresses developments in the precise manipulation of POSS building blocks via atom transfer radical polymerization, reversible addition-fragmentation chain transfer, and click chemistry. Not only are the structures of POSS-hybrid polymers tunable in terms of chemical composition, molecular weight, and polydispersity, but they are also controllable in sequential and hierarchical chain topology. Finally, some representative cutting-edge applications of POSS-hybrid polymers, including biomedical and energy-related materials, fabrication of nanostructures, and functional surface coating materials, are highlighted.

A 3D nanoscale polyhedral oligomeric silsesquioxanes network for microextraction of polycyclic aromatic hydrocarbons.

Polyhedral oligomeric silsesquioxanes are 3D nanoscaled materials with large potential in solid phase microextraction (SPME). Here, as a case study, an octaglycidyldimethylsilyl modified polyhedral oligomeric silsesquioxane network is described. It was deposited on a stainless steel wire via a sol-gel method and used as a fiber coating for SPME of aromatic compounds. The uniform pore structure, high surface area, and hydrophobicity of the network make it susceptible toward isolation of non-polar and semi-polar chemical compounds. The performance of the fiber coating was tested with three classes of environmental pollutants, viz. chlorobenzenes (CBs), benzenes (benzene, toluene, ethylbenzene, xylene; known as BTEX), and polycyclic aromatic hydrocarbons. The effects of various types of sol-gel precursors on the fabrication and performance of fiber coatings were investigated. The extraction capability of the fiber coating was compared with the polydimethyl siloxane/divinylbenzene based commercial fiber. Parameters affecting headspace analysis and gas chromatographic quantitation were optimized. The method was applied to the quantification of PAHs, as model analytes, in tea, coffee and some environmental waters. Linear responses typically cover the 1-200 ng·L-1 concentration range, limits of detection are between 0.1 and 0.3 ng·L-1, intra-day relative standard deviation are <10%, and inter-day RSDs are <12%. The fiber has a long lifespan and can be used >200 times. Graphical abstract Schematic presentation of a headspace solid phase microextraction process which is implemented to the analysis of PAHs in tea and coffee samples. The SEM image of the SPME fiber coating, the 3D nanoscale polyhedral oligomeric silsesquioxane (POSS) network, and the POSS-epoxy molecular structure are shown.

Molecularly imprinted polymer prepared with polyhedral oligomeric silsesquioxane through reversible addition-fragmentation chain transfer polymerization.

Polyhedral oligomeric silsesquioxane (POSS) was utilized to prepare imprinted polymer through reversible addition-fragmentation chain transfer polymerization (RAFT) successfully. The imprinted polymer was made with a mixture of RAFT agent, 4-vinylpyridine (4-VP), POSS monomer [PSS-(1-propylmethacrylate)-heptaisobutyl substituted, MA 0702], and ethylene glycol dimethacrylate (EDMA), with ketoprofen (KET) as template. The influence of polymerization variables, the amount of RAFT agent and POSS monomer, the ratio of KET to 4-VP, and the ratio of 4-VP to EDMA, were investigated on the retention factor and imprinting effect. The greatest imprinting factor of the RAFT agent-based POSS MIP was 15.2, about 1.5 times higher than the RAFT agent-free agent POSS MIP. The permeability, surface morphology, as well as pore size distribution of POSS MIP monoliths made with RAFT agent and without RAFT agent were also studied. The optimal MIP was applied to solid phase extraction for KET from commercial tablets. The mean recoveries of KET for RAFT-based POSS MIP was 85.2% with a relative standard deviation of 2.6%.

Reactive Hybrid of Polyhedral Oligomeric Silsesquioxane (POSS) and Sulfur as a Building Block for Self-Healing Materials.

This work demonstrates a new reactive and functional hybrid (S-MMA-POSS) of polyhedral oligomeric silsesquioxane (POSS) and sulfur prepared with a direct reaction between a multifunctional methacrylated POSS compound (MMA-POSS) and elemental sulfur (S8 ) through the "inverse vulcanization" process. S-MMA-POSS is an effective building block for imparting self-healing ability to the corresponding thermally crosslinked POSS-containing nanocomposites through a self-curing reaction and co-curing reaction with conventional thermosetting resins. Moreover, S-MMA-POSS is also a useful precursor for preparation of materials with high transparency in mid-infrared region.