Qingqing Dou

Multi-functional fluorescent carbon dots with antibacterial and gene delivery properties†

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.

Effective near-infrared photodynamic therapy assisted by upconversion nanoparticles conjugated with photosensitizers

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-dimethylth-iazol-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 (50 μg mL(-1)) of this nanocomplex and mild dosage (7 mW cm(-2)) of near-infrared laser treatment.

Tuning of the structure and emission spectra of upconversion nanocrystals by alkali ion doping.

Recently, lanthanide based nanocrystals with upconversion fluorescence emission have attracted a lot of interest and the nanocrystals have been used for bioimaging, biodetection, and therapeutic applications. Use of the nanocrystals for multiplexed detection has also been explored; however, nanocrystals with multicolor emission are required. Some efforts have been made to tune the emission spectra of the nanocrystals based on manipulation of upconverting lanthanide ions doped in the crystals or creation of core/shell structures. In this work, alkali ions with an ionic radius slightly larger or smaller than Na such as Li and K were doped into NaYF(4):Yb,Er nanocrystals and their effect on the crystal structure and subsequently the upconversion emission spectra were studied. It was found that the phase transition occurs in the nanocrystals when a different amount of Li and K was doped. Furthermore, the intensity ratios between the blue, green, and red emission peaks changed accordingly, and make it possible to tune the upconversion fluorescence of the nanocrystals by Li and K doping.

Nanomaterial mediated optogenetics: opportunities and challenges

Optogenetics is a promising neuronal modulation strategy in neuroscience, which enables real-time neuromodulation in free-moving animals with high spatiotemporal control. However, it still suffers from several disadvantages, including low penetration of excitation light and the invasiveness of the insertion of the light delivery system. The incorporation of nanomaterials with different properties into optogenetics may bring new opportunities to solve the problems encountered in optogenetics, from the delivery/expression of the optogene to the stimulation/inhibition and follow-up sensing of neural activity. The challenges of nanomaterial-mediated optogenetics are also discussed. This review elaborates on the feasibility of incorporating nanomaterials into optogenetics and analyzes the benefits of nanomaterial-mediated optogenetics.

Sandwich-structured upconversion nanoparticles with tunable color for multiplexed cell labeling

The need for a more efficient biological label to meet their burgeoning utility in rapidly developing multiplexing applications may be realized through the recent advent of upconversion nanoparticles (UCNs). UCNs fabricated to-date, however, are either not displaying strong fluorescence or have limited available colors. Here, we report on fabricating sandwich-structured UCNs with a NaYbF(4) matrix sandwiched between two NaYF(4) layers. Such sandwich design allows for efficient absorption of the excitation energy by the absorber ion-rich NaYbF(4) layer that then transfers it to the adjacent NaYF(4) layers on either side for an improved fluorescence efficiency. By doping different emitters into each of the shells and adjusting their thickness, different color output tunable based on the RGB color model were obtained. In this study, multicolor UCNs with strong emission intensity have been facilely synthesized and used for multiplex detection of three subcellular targets with a single near-infrared excitation wavelength.

Long-Term Real-Time In Vivo Drug Release Monitoring with AIE Thermogelling Polymer

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.

Biodegradable Thermogelling Polymers: Working Towards Clinical Applications

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.

Emerging Supramolecular Therapeutic Carriers Based on Host–Guest Interactions

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.

New Linear and Star‐Shaped Thermogelling Poly([R]‐3‐hydroxybutyrate) Copolymers

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 (1) H and (13) C 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.

Multi-arm carriers composed of an antioxidant lignin core and poly(glycidyl methacrylate-co-poly(ethylene glycol)methacrylate) derivative arms for highly efficient gene 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.