Synthesis of Starch-Based Amphiphilic Fluorescent Nanoparticles and Their Application in Biological Imaging.

Due to the extensive source, good biocompatibility and biodegradability, the starch of carbohydrates has been extensively investigated for application in biological field. Recently, the development of fluorescent organic nanoparticles (FONs) on the basis of aggregation induced emission (AIE) dyes has attracted great research interest. In this article, novel starch-based S-TPEV polymers with AIE property were successfully fabricated by atom transfer radical polymerization (ATRP) of TPEV dye into water-soluble starch for the first time, subsequently, their structure and properties were detailedly investigated by 1H NMR, TEM, UV-vis, FL and FTIR. The characterization results confirmed the successful synthesis of S-TPEV polymers, and the molar fraction of TPEV and C6H10O5 ring in the starch polymers could be respectively calculated as approximate 5.8% and 94.2%. In aqueous solution, the as-prepared S-TPEV polymers will tend to self-assemble into FONs with 100-200 nm diameters, and their fluorescence intensity increased with the increase of the concentration of water in the mixed solution of water and DMSO, indicative of the obvious AIE property. More importantly, owing to their high water dispersity, good fluorescence and excellent biocompatibility, the S-TPEV FONs can be uptaken by HepG2 cells and show promising application in biological imaging field.

Aggregation Induced Emission Fluorogens Based Nanotheranostics for Targeted and Imaging-Guided Chemo-Photothermal Combination Therapy.

Nanotheranostics for biomedical imaging-guided cancer therapy have attracted increasing interest due to their capabilities of both precise tumor diagnosis and high therapeutic efficacy. Among the diverse imaging models, fluorescence imaging have been extensively researched for their high sensitivity, simple operation, and low cost. In this work, aggregation induced emission (AIE) fluorogens based targeted nanotheranostics are facilely fabricated via paclitaxel (PTX) induced assembly of proteins for the first time. Thanks to the unique fluorescence property of AIE fluorogens PhENH2 , the prepared theranostic nanoplatforms can emit bright fluorescence even after being incorporated with the photothermal therapy agent polypyrrole (PPy), which will often decrease or quench the emission of common fluorescence dyes. The target moiety of cyclic arginine-glycine-aspartic acid (cRGD) endows the nanotheranostics with outstanding targeting ability, which can further facilitate the targeted imaging and cancer treatment. As revealed by the in vitro and in vivo experiments, the prepared nanotheranostics human serum albumin-PhENH2 -PPy-PTX-cRGD shows impressive performance in the targeted fluorescence imaging even after intravenous injection for 48 h, and their combined chemo-photothermal therapy is also very effective. These results indicate that AIE fluorogens based nanotheranostics would find a promising prospect in further improved multimodal imaging and imaging guided cancer treatment.

Synthesis of an aggregation-induced emission (AIE) dye with pH-sensitivity based on tetraphenylethylene-pyridine for fluorescent nanoparticles and its applications in bioimaging and in vitro anti-tumor effect.

In this contribution, a novel AIE monomers 2-(4-styrylphenyl)- 1,2-diphenylvinyl)styryl)pyridine (SDVPY) with smart fluorescent pH-sensitivity basing on tetraphenylethylene-pyridine were successfully synthesized for the first time, subsequently, a series of amphiphilic copolymers PEG-PY were achieved by reversible addition-fragmentation chain transfer (RAFT) polymerization of SDVPY and poly(ethylene glycol) methacrylate (PEGMA), which would self-assemble in water solution to form core-shell nanoparticles (PEG-PY FONs) with about 150 nm diameter. The PEG-PY FONs showed obvious fluorescence response to Fe3+, HCO3- and CO32- ions in aqueous solution owing to their smart pH-sensitivity and AIE characteristics, and their maximum emission wavelength could reversibly change from 525 nm to 624 nm. The as-prepared PEG-PY FONs showed also prospective application in cells imaging with the variable fluorescence for different pH cells micro-environment. When PEG-PY copolymers self-assembled with the anti-tumor drug paclitaxel (PTX), the obtained PY-PTX FONs could effectively deliver and release PTX with pH-sensitivity, and could be easily internalized by A549 cells and located at the cytoplasm with high cytotoxicity, which was further confirmed by the Calcein-AM/PI staining of dead and alive A549 cells. Moreover, the flow cytometry results indicated that the PY-PTX FONs could obviously induce the apoptosis of A549 cells, which further showed the great potential of PY-PTX FONs in the application of tumors therapy.

An acrylate AIE-active dye with a two-photon fluorescent switch for fluorescent nanoparticles by RAFT polymerization: synthesis, molecular structure and application in cell imaging.

Recently, AIE-active fluorescent materials have attracted extensive investigation due to their significant applications in the fields of memory devices, photomodulation, information displays, sensors, and biological imaging. In this contribution, a novel acrylate AIE-active dye of TPMA was successfully synthesized by Suzuki coupling and acylation reaction, and belongs to the monoclinic crystal system and P21/c space group from the crystal structure analysis, and its fluorescence intensity was stronger with an obvious red shift of emission wavelength as compared with the reported TPB dye. Moreover, the obtained TPMA dye exhibits multi-stimuli-responsivity and a two-photon fluorescent switch with excellent reversibility in the solid state. Subsequently, the corresponding fluorescent polymers of PEG-TM were successfully fabricated via RAFT polymerization of TPMA and PEGMA with a molecular weight of about 25 000 (M n) and narrow polydispersity index (PDI). From 1H NMR analysis, when the feeding ratio of TPMA increased to 32.2% from 19.2%, the molar fraction of TPMA in PEG-TM polymers accordingly increased to 32.8% from 19.5%. In water solution, the as-prepared PEG-TM1 polymers would self-assemble into fluorescent organic nanoparticles (FONs) with diameters ranging from 150 to 250 nm, and their maximum emission wavelength presented at 518 nm with obvious AIE phenomena. Moreover, the as-synthesized PEG-TM polymers have prospective application in biological imaging due to their good fluorescence, high water solubility and excellent biocompatibility.

A novel AIE-active dye for fluorescent nanoparticles by one-pot combination of Hantzsch reaction and RAFT polymerization: synthesis, molecular structure and application in cell imaging.

In recent years, amphiphilic AIE-active fluorescent organic materials with aggregation-induced emission (AIE) properties have been extensively investigated due to their excellent properties. This study describes the synthesis of a novel AIE-active dye of tetraphenylethylene diphenylaldehyde (TPDA). As compared with the reported fluorescent dye TPB, the fluorescence intensity of TPDA is significantly enhanced with the distinct red shift of emission wavelength. Subsequently, the corresponding novel polymers PEG-TPD were obtained through the one-pot combination of Hantzsch reaction and RAFT polymerization. The structure of PEG-TPD1 by the two-step process was similar with that of PEG-TPD2 by the one-pot method at the same feeding ratio of TPDA and PEGMA. The molecular weights (M n) of the polymers PEG-TPD1 and PEG-TPD2 were respectively 52 000 and 28 000 with narrow polydispersity index (PDI), and their molar fractions of TPDA were respectively about 9.5% and 14.3%, indicating that the degree of Hantzsch reaction in the one-pot process was more complete. Subsequently, the effect of feed ratio of TPDA and PEGMA on polymer structure was further studied. It can be seen that the M n of the polymers gradually increases as the proportion of TPDA increases. In aqueous solution, these amphiphilic PEG-TPD polymers tended to self-assemble into corresponding fluorescent polymer nanoparticles (FPNs). The diameter of PEG-TPD2 FPNs ranged from 200 to 300 nm, and their fluorescence emission spectra have maximum emission peak at 509 nm. The PEG-TPD FPNs have significant advantages such as good fluorescence intensity, high water dispersibility, good biocompatibility and easy absorption by cells, which can be attractively used in the field of bioimaging.

One-pot preparation of cross-linked amphiphilic fluorescent polymer based on aggregation induced emission dyes.

Facile one-pot preparation of cross-linked amphiphilic fluorescent polymer based on aggregation induced emission (AIE) dyes and 2-isocyanatoethyl methacrylate (IM) has been developed. This was carried out first by free radical polymerization between AIE monomer (PhE) and IM, and then polyethyleneimine (PEI) was introduced to obtain the cross-linked fluorescent polymer. The resulted cross-linked amphiphilic polymer was prone to self-assemble into stable nanoparticles in aqueous solution with surplus amino groups on the surface which made them highly water dispersible and can be further functionalized. The as-prepared fluorescent polymer nanoparticles (PhE-IM-PEI FPNs) were fully characterized by a series of techniques including (1)H NMR spectrum, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, dynamic light scattering, UV-vis absorption spectrum, and fluorescence spectra. Such FPNs demonstrated intense orange fluorescence with a high quantum yield of about 40%. Biocompatibility evaluation and cell uptake behavior of the nanoparticles were further investigated to explore their potential biomedical applications; the demonstrated excellent biocompatibility made them promising for cell imaging.

Zwitterionic red fluorescent polymeric nanoparticles for cell imaging.

Phospholipid monomer and aggregation-induced emission (AIE) dye-based dimers are incorporated via reversible addition-fragmentation transfer polymerization to afford cross-linked zwitterionic fluorescent copolymers. Such copolymers are prone to self-assembly into fluorescent polymeric nanoparticles (FPNs) in physiological solution due to their amphiphilic nature. Characterization of these red FPNs by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy indicates the successful preparation of these zwitterionic copolymers. UV-visible absorption spectroscopy, fluorescence spectroscopy, transmission electron microscopy, and dynamic light scattering are performed to demonstrate the bright red fluorescence of the FPNs and their stable dispersibilities, even below the critical micelle concentration in physiological solution. Finally, studies of the biocompatibility and cell uptake behavior of the FPNs are conducted and show excellent biocompatibility for cell imaging application.