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The incorporation of nanofillers into polymeric matrix has been proven to be an effective route to reinforce their mechanical properties, and the usage of binary fillers that combines the advantages of the two fillers could lead to further property enhancement. In this work, binary nanofillers consist of multi-walled carbon nanotubes (MWCNTs)-bridged fumed silica (FSiO2) were synthesized for the first time by Pt coupling reaction of methyldiethoxysilane (MDES) modified MWCNTs and triethoxyvinylsilane (TEVS) functionized SiO2, in which MDES modified MWCNTs was synthesized by reacting OH-functionized MWCNTs with MDES, while TEVS-FSiO2 was obtained by reacting fume silica with TEVS. The binary MWCNTs-bridged-FSiO2 was introduced into liquid silicone rubber (LSR) for mechanical reinforcement. It is shown that the interfacial interaction between binary fillers and LSR matrix is significantly enhanced due to the chemical bridging as well as the excess TEVS molecules on SiO2, and the Young's modulus, tensile strength and tear strength of the LSR could be increased by 64%, 29% and 52%, respectively, with incorporation of only 0.25 phr of MWCNTs for the binary fillers. The observed mechanical enhancement could be attributed to good interfacial interaction between the fillers and LSR due to the existence of SiO2 (with excess matrix compatible molecules) on the surface of MWCNTs, which facilitate the filler dispersion in LSR matrix and the promote stress transfer from matrix to MWCNTs, as well as the advantages of extremely high aspect ratio and excellent mechanical strength of MWCNTs.

Dilute acid polymerizes degassed, aqueous acrylamide with concomitant gelation, without the need for added free radical initiator or cross-linking agent. This reaction is accelerated by sonication or UV irradiation, but inhibited by adventitious oxygen or the addition of a free radical inhibitor, suggesting an acid-accelerated free radical process. The resulting hydrogels are thixotropic in nature and partially disrupted by the addition of chaotropic agents, indicating the importance of hydrogen bonding to the 3D network. This discovery was made while trying to prepare pectin-polyacrylamide hydrogels. We observed that pectin initiated the gelation of acrylamide, but only if the aqueous pectin samples had a pH lower than ca. 5.

A porous tough hydrogel (alginate–polyacrylamide) is successfully synthesized using a photo-gelling polymer as a templating agent. Unlike current porous hydrogels, we present a useful pore-enhancing strategy without sacrificing the mechanical properties of the parent matrix. These porous tough hydrogels, as 3D cell culture scaffolds, can mimic the extracellular matrix and allow maximum nutrient exchange.

Recent advances in host-guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non-covalent interactions provide vast possibilities of manipulating supramolecular self-assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self-assemblies through host-guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli-responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co-delivery and site-specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host-guest chemistry with biological interface science are proposed.

In situ gel delivery systems are preferred over conventional systems due to sustained and prolonged release action of therapeutic payload onto the targeted site. Thermogel, a form of in situ gel-forming polymeric formulation, undergoes sol-gel transition after administration into the body. At room temperature, the system is an aqueous polymer solution that easily entraps therapeutic payload by mixing. Upon injection, the higher physiological temperature causes gelation in situ because of the presence of thermosensitive polymers. The gel degrades gradually over time, allowing sustained release of therapeutics localized to the site of interest. This minimizes systemic toxicity and improved efficacy of drug release to the targeted site. Thermogel properties can be easily altered for specific applications via substitution and modification of components in diblock and triblock copolymer systems. The feasibility of fine-tuning allows modifications to biodegradability, biocompatibility, biological functionalization, mechanical properties, and drug release profile. This review summarized recent development in thermogel research with a focus on synthesis and self-assembly mechanisms, gel biodegradability, and applications for drug delivery, cell encapsulation and tissue engineering. This review also assessed inadequacy of material properties as a stand-alone factor on therapeutic action efficacy in human trials, with a focus on OncoGel, an experimental thermogel that demonstrated excellent individual or synergistic drug delivery system in preclinical trials but lacked therapeutic impact in human trials. Detailed analysis from all aspects must be considered during technology development for a successful thermogel platform in drug delivery and tissue engineering.

We report on the conversion of n-type InN thin films on top of III-nitride heterostructures to p-type β-In2S3 by post-growth heat treatments in a sulfur-vapor environment and address their photoelectrical and photocatalytic properties for functional integrations. Their electrical, structural, and spectroscopic evolutions as a function of sulfurization temperatures reveal an onset of surface passivation of InN at low temperatures (i.e., T < 550 °C) and the passivation is less effective at high temperatures. The conversion of InN to β-In2S3 starts at T ≥ 700 °C; the conversion increases with the sulfurization temperature and completes at T = 750 °C; and a further increase in the sulfurization temperature leads to a conversion of β-In2S3 to In2O3 due to the exhaustion of sulfur. The coherently strained InGaN buffer underneath the InN overlayer of the heterostructure is intact even at T = 800 °C. Photocurrent measurements do not show any apparent light responses for the thin films until sulfurized at T ≥ 700 °C while the photocatalytic degradation tests of rhodamine B (RhB) under visible irradiations (λ ≥ 400 nm) provide evidence for deethylation of RhB to DMRh (N,N-diehyl-N′-ethyl-rhodamine 110) on the surface of the thin films with higher activities on n-type InN and In2O3 than that on p-type β-In2S3 films. These observations, together with the intact InGaN underneath, open up a novel way to monolithic integrations of β-In2S3/InN based optical/photochemical sensors with GaN-based electronic devices (e.g., high-electron-mobility transistors) for advanced applications.

In this study, we report the synthesis and characterisation of a thermogelling poly(carbonate urethane) system comprising poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG) and poly(polytetrahydrofuran carbonate) (PTHF carbonate). The incorporation of PTHF carbonate allowed for the control of the lower critical solution temperature (LCST) and decreased critical gelation concentration (CGC) of the thermogels significantly. In addition, the as-prepared thermogels displayed low toxicity against HepG2, L02 and HEK293T cells. Drug release studies were carried out using doxorubicin (Dox). Studies conducted using nude mice models with hepatocellular carcinoma revealed that the Dox-loaded poly(PEG/PPG/PTHF carbonate urethane) thermogels showed excellent in vivo anti-tumour performance and effectively inhibited tumour growth in the tested model.

Glucose is abundant in nature and can be found in various sources. In this study, we developed multifunctional carbon dots (CDs) with glucose and poly(ethyleneimine) (PEI), which were further quaternized using a facile approach. The CDs are designed to possess both anti-bacteria and gene delivery capabilities. The inherent property was characterized with TEM, NMR, FTIR and fluorescent spectroscopy. Antibacterial activity was evaluated with Broth minimum inhibitory concentration (MIC) assay on both Gram-positive and Gram-negative bacteria. The CDs showed excellent inhibitation to both bacteria. The expression of CDs condensed plasmid DNA in HEK 293T cells was investigated with luciferase expression assay. Gene transfection capability of the quaternized CDs was found to be up to 104 times efficient than naked DNA delivery.

A lignin-based copolymer with good biocompability was successfully prepared via atom transfer radical polymerization (ATRP) for efficient gene delivery. Kraft lignin was modified into lignin-based macroinitiators and then poly(glycidyl methacrylate)-co-poly(ethylene glycol)methacrylate (PGMA-PEGMA) side chains were prepared via ATRP grafting onto lignin. Ethanolamine was sequentially functionalized onto lignin-PGMA-PEGMA and a cationic lignin-PGEA-PEGMA copolymer consisting of a lignin core and different-length PGEA-PEGMA side chains was produced. Lignin-PGEA-PEGMA copolymers could efficiently compact pDNA into nanoparticles with sizes ranging from 150 to 250 nm at N/P ratios of 10 or higher. The gene transfection efficiency depends greatly on the mass percentage of PGEA units and the N/P ratio. The lignin-PGEA-PEGMA with 46.9% (mass%) of PGEA units (i.e. LG100) has highest transfection efficiency in comparison with the copolymers with a lower amount of PGEA units. In addition, LG100 has high transfection efficiency under serum conditions, which is comparable to or much higher than PEI control in HEK 293T and Hep G2 cell lines. More importantly, lignin-PGEA-PEGMA copolymers have excellent antioxidant activity. The novel cationic lignin-PGEA-PEGMA copolymers can be promising gene carriers for gene delivery.

Upconversion nanoparticles (UCNs) attract intensive attentions in biomedical applications. They have shown great potential in bioimaging, biomolecule detection, drug delivery, photodynamic therapy and cellular molecules interactions. Due to the anti-Stokes optical property and NIR excitation, UCNs overcome the drawbacks encountered in conventional luminescent biomarkers. High signal to noise ratio, low cytotoxicity and stable high throughput results are obtained using UCNs as luminescent labels or light triggers in biomedical applications. In this review article, the reason for choosing UCNs as biomedical agents, the progress of the UCNs development and case studies of their biomedical applications will be discussed.

As society ages, aging medical problems such as organ damage or failure among senior citizens increases, raising the demand for organ repair technologies. Synthetic materials have been developed and applied in various parts of human body to meet the biomedical needs. Hydrogels, in particular, have found extensive applications as wound healing, drug delivery and controlled release, and scaffold materials in the human body. The development of the next generation of soft hydrogel biomaterials focuses on facile synthetic methods, efficacy of treatment, and tunable multi-functionalities for applications. Supramolecular 3D entities are highly attractive materials for biomedical application. They are assembled by modules via various non-covalent bonds (hydrogen bonds, p-p stacking and/or van der Waals interactions). Biodegradable thermogels are a class of such supramolecular assembled materials. Their use as soft biomaterials and their related applications are described in this Review.

Thermogels are stimuli-responsive soft materials which undergo sol–gel transition with temperature changes. The gel is fluid at room temperature and can be blended with therapeutics by mixing. The higher physiological temperature that a gel encounters upon injection results in gelation due to the presence of thermosensitive polymers. The degradation of the gel allows sustained release of therapeutics localized to the site of interest. Thermogel properties, such as biodegradability, biocompatibility, biological functionalization, mechanical properties and the therapeutic release profile, can be fine-tuned via the substitution and modification of components in these diblock and triblock copolymer systems. This chapter examines the key concepts behind the technology development of these thermogels to successfully translate thermogels for therapeutic conveyance and tissue repair and replacement.

Recent advances in host-guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non-covalent interactions provide vast possibilities of manipulating supramolecular self-assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self-assemblies through host-guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli-responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co-delivery and site-specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host-guest chemistry with biological interface science are proposed.

International audience; The synthesis of multi-arm poly([R]-3-hydroxybutyrate) (PHB)-based triblock copolymers (poly([R]-3-hydroxybutyrate)-b-poly(N-isopropylacrylamide)-b-[[poly(methyl ether methacrylate)-g-poly(ethylene glycol)]-co-[poly(methacrylate)-g-poly(propylene glycol)]], PHB-b-PNIPAAM-b-(PPEGMEMA-co-PPPGMA), and their subsequent self-assembly into thermo-responsive hydrogels is described. Atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAAM) followed by poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and poly(propylene glycol) methacrylate (PPGMA) was achieved from bromoesterified multi-arm PHB macroinitiators. The composition of the resulting copolymers was investigated by 1H and 13C J-MOD NMR spectroscopy as well as size-exclusion chromatography (SEC), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The copolymers featuring different architectures and distinct hydrophilic/hydrophobic contents were found to self-assemble into thermo-responsive gels in aqueous solution. Rheological studies indicated that the linear one-arm PHB-based copolymer tend to form a micellar solution, whereas the two- and four-arm PHB-based copolymers afforded gels with enhanced mechanical properties and solid-like behavior. These investigations are the first to correlate the gelation properties to the arm number of a PHB-based copolymer. All copolymers revealed a double thermo-responsive behavior due to the NIPAAM and PPGMA blocks, thus allowing first the copolymer self-assembly at room temperature, and then the delivery of a drug at body temperature (37 °C). The non-significant toxic response of the gels, as assessed by the cell viability of the CCD-112CoN human fibroblast cell line with different concentrations of the triblock copolymers ranging from 0.03 to 1 mg mL−1, suggest that these PHB-based thermo-responsive gels are promising candidate biomaterials for drug-delivery applications.

The induction of autophagy on exposure of cells to a variety of nanoparticles represents both a safety concern and an application niche for engineered nanomaterials. Here, we show that a short synthetic peptide, RE-1, identified by means of phage display, binds to lanthanide (LN) oxide and upconversion nanocrystals (UCN), forms a stable coating layer on the nanoparticles' surface, and effectively abrogates their autophagy-inducing activity. Furthermore, RE-1 peptide variants exhibit a differentially reduced binding capability, and correspondingly, a varied ability to reduce the autophagic response. We also show that the addition of an arginine-glycine-aspartic acid (RGD) motif to RE-1 enhances autophagy for LN UCN through the interaction with integrins. RE-1 and its variants provide a versatile tool for tuning material-cell interactions to achieve the desired level of autophagy, and may prove useful for the various diagnostic and therapeutic applications of LN-based nanomaterials and nanodevices.

A new drug concentration meter is developed. In vivo drug release can be monitored precisely via a self-indicating drug delivery system consisting of a new aggregation-induced emission thermoresponsive hydrogel. By taking the advantage of a self-indicating system, one can easily detect the depletion of drugs, and reinject to maintain a dosage in the optimal therapeutic window. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

Qing Qing Dou,1 Choon Peng Teng,1 Enyi Ye,1 Xian Jun Loh1–3 1Institute of Materials Research and Engineering, A*STAR, Singapore; 2Department of Materials Science andEngineering, National University of Singapore, Singapore; 3Singapore Eye Research Institute, Singapore Abstract: A drug model photosensitizer–conjugated upconversion nanoparticles nanocomplex was explored for application in near-infrared photodynamic therapy. As near-infrared penetrates deeper into the tissue, the model is useful for the application of photodynamic therapy in deeper tissue. The nanocomplex that was synthesized had low polydispersity, and the upconversion nanoparticle was covalently conjugated with the photosensitizer. The robust bond could prevent the undesired premature release of photosensitizer and also enhance the singlet-oxygen generation. Singlet-oxygen generation rate from this nanocomplex was evaluated in solution. The photodynamic therapy effect was assessed with MCF-7 cells in two different methods, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead assay. The assay results showed that promising efficacy (>90%) can be achieved with a low concentration (50µgmL-1) of this nanocomplex and mild dosage (7mWcm-2) of near-infrared laser treatment. Keywords: nanocomplex, singlet-oxygen generation rate, MTT assay, live/dead assay

Core-shell nanoparticles (CSNPs) with diverse chemical compositions have been attracting greater attention in recent years. However, it has been a challenge to develop CSNPs with different crystal structures due to the lattice mismatch of the nanocrystals. Here we report a rational design of core-shell heterostructure consisting of NaYF4:Yb,Tm upconversion nanoparticle (UCN) as the core and ZnO semiconductor as the shell for potential application in photodynamic therapy (PDT). The core-shell architecture (confirmed by TEM and STEM) enables for improving the loading efficiency of photosensitizer (ZnO) as the semiconductor is directly coated on the UCN core. Importantly, UCN acts as a transducer to sensitize ZnO and trigger the generation of cytotoxic reactive oxygen species (ROS) to induce cancer cell death. We also present a firefly luciferase (FLuc) reporter gene based molecular biosensor (ARE-FLuc) to measure the antioxidant signaling response activated in cells during the release of ROS in response to the exposure of CSNPs under 980 nm NIR light. The breast cancer cells (MDA-MB-231 and 4T1) exposed to CSNPs showed significant release of ROS as measured by aminophenyl fluorescein (APF) and ARE-FLuc luciferase assays and ~45% cancer cell death as measured by MTT assay, when illuminated with 980 nm NIR light.

The synthesis and gene transfection efficiency of a series of amphiphilic copolymers, poly(2-(dimethylamino)ethyl methacrylate)-poly (methacrylate isobutyl polyhedral oligomeric silsesquioxane) (PDMAEMA-POSS) copolymers are reported. The hydrophobic POSS interior allows a cell-sensitizing drug such as paclitaxel to be incorporated, whereas the cationic and hydrophilic PDMAEMA corona allows the complexation of anionic DNA to form a nano-sized polyplex. These drug-encapsulated copolymers display excellent gene transfection efficiency compared with polyethylenimine or PDMAEMA homopolymers.