Chao Yin

Oligo(p-phenyleneethynylene) embedded amphiphiles: synthesis, photophysical properties and self-assembled nanoparticles with high structural stability and photostability for cell imaging

Novel amphiphilic organic asymmetrically oligo(p-phenyleneethynylene) (OPE) conjugated molecules, ending with a hydrophobic alkyl chain and a hydrophilic methoxypolyethyleneglycol (MPEG) segment, were designed and synthesized. Due to the hydrophilic–hydrophobic nature of the asymmetrically amphiphilic OPE conjugated molecules, monodispersed fluorescent nanoparticles were obtained easily by self-assembly in aqueous solution. Through adjusting the length of MPEG chains in amphiphilic OPE, a series of nanoparticles with different water solubility were prepared. The aggregation behaviors of these dyes were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), which indicated that when the MPEG chains bonding with amphiphilic OPE are longer, smaller sized nanoparticles will be formed at the same concentration of 10−5 mol L−1. Besides, taking OPE–PEG1900 as an example, diversified aggregation behaviors under different concentrations can be inferred through DLS and TEM, which were also supported by ultraviolet absorption (UV) and photoluminescence (PL) analyses. Compared with previously reported conjugated-polymer nanoparticles consisting of amphiphiles without photoelectric features and oil-soluble conjugated-polymers through non-covalent encapsulation, the introduction of OPE chromophores into amphiphiles by covalent linkage efficiently enhanced the structural stability of nanoparticles. A photobleaching test under UV excitation revealed the high photostability of these OPE nanoparticles. In view of the good water solubility, biocompatibility, structural stability, photostability, and excellent photoelectric features of these nanoparticles, cellular imaging of human pancreatic cancer cells (PANC-1 cells) was conducted. Confocal microscopy results showed that the nanoparticles (OPE–PEG1000 and OPE–PEG1900) were located specifically within the cell cytoplasm. We believe that the OPE nanoparticles would play an important role as fluorescent biomarkers for long-term bioimaging, and offer new opportunities for good applicability in cell imaging and sensing in biomedical science.

O-Nitrobenzyl-alt-(phenylethynyl)benzene copolymer-based nanoaggregates with highly efficient two-photon-triggered degradable properties via a FRET process

Light-controlled drug delivery systems constituted an appealing means to realize drug release spatiotemporally at the site of interest with high specificity. However, the utilization of light-activatable systems was hindered by the lack of suitable drug carriers that respond to near infrared light. Here, we reported a two-photon-triggered degradable amphiphilic copolymer in which the photo-cleavable species o-nitrobenzyl (ONB) was positioned alternately into the backbone of a (phenylethynyl)benzene (PEB) based polymer. Further, hydrophilic polyethylene glycol was grafted onto the side chain of the copolymer to obtain an amphiphilic structure, which could self-assemble into nanoaggregates (NAs). The state of NAs was unambiguously demonstrated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In this structure, the PEB fluorophore with a relatively good two-photon absorption (TPA) cross-section performed fluorescence resonance energy transfer (FRET) to ONB under 800 nm irradiation for two-photon-triggered photolysis. The aggregation state of copolymer NAs provided a large TPA cross-section and effective intermolecular/intramolecular FRET between PEB and ONB, which was beneficial for improving the degradation efficiency. As a proof of concept, a hydrophobic drug (Nile Red) was encapsulated into the NAs via a self-assembly method and was successfully released due to the photo-destruction of copolymer NAs upon two-photon excitation, thereby providing a variety of potential applications in two-photon-responsive drug delivery.

A macrocyclic oligoelectrolyte as a facial platform for absorbing hyaluronic acid oligomers for targeted cancer cellular imaging

A novel water-soluble macrocyclic oligoelectrolyte (MOE) was designed and synthesized by a simple Friedel–Crafts reaction as a facial platform for fabricating biological nanoparticles. The produced MOE with a unique three-dimension (3D) rigid structure consisted of a triphenylamine-based cyclic core and three oligofluorene arms, which protruded from the ring plane on both sides. The specific structure rendered MOE with good photoluminescence (PL) stabilities, low aggregation tendencies and excellent water-soluble properties in the form of well-defined smart organic dots (sub-10 nm) in aqueous solution. Using these organic dots as a template and OHAs, a biocompatible and linear oligosaccharide made straightforward contact with CD44 (a principal cell surface receptor for HA). As a stabilizer and biomarker, functional nanoparticles (MHNs-0.4) were fabricated via electronic interaction induced self-assembly in aqueous solution. The final confirmed MHNs-0.4 with suitable size (around 80 nm), good stability and fluorescent properties were found to be outstanding materials for the specific labelling of CD44-overexpressed human lung cancer cells (A549). The highlight of the study is that we provided a powerful and reliable platform, MOE-dots, for adsorbing various negatively charged molecules and broadening potential biological applications.

A Single Composition Architecture-Based Nanoprobe for Ratiometric Photoacoustic Imaging of Glutathione (GSH) in Living Mice

As one of the reduction species, glutathione (GSH) plays a tremendous role in regulating the homeostasis of redox state in living body. Accurate imaging of GSH in vivo is highly desired to provide a real-time visualization of physiological and pathological conditions while it is still a big challenge. Recently developed photoacoustic imaging (PAI) with high resolution and deep penetration characteristics is more promising for in vivo GSH detection. However, its application is dramatically limited by the difficult designation of photoacoustic probes with changeable near-infrared (NIR)-absorption under reductive activation. A cyanine derivative-based activatable probe is developed for in vivo ratiometric PAI of GSH for the first time. The probe is structurally designed to output ratiometric signals toward GSH in NIR-absorption region based on the cleavage of disulfide bond followed by a subsequent exchange between the secondary amine and sulfydryl group formed. Such a ratiometric manner provides high signal-to-noise imaging of blood vessels and their surrounding areas in tumor. Concomitantly, it also exhibits good specificity toward GSH over other thiols. Furthermore, the single composition architecture of the probe effectively overcomes the leakage issue compared with traditional multicomposition architecture-based nanoprobe, thus enhancing the imaging accuracy and fidelity in living body.

Activatable Semiconducting Theranostics: Simultaneous Generation and Ratiometric Photoacoustic Imaging of Reactive Oxygen Species In Vivo

Enhancing the generation of reactive oxygen species (ROS) is an effective anticancer strategy. However, it is a great challenge to control the production and to image ROS in vivo, both of which are vital for improving the efficacy and accuracy of cancer therapy. Herein, an activatable semiconducting theranostic nanoparticle (NP) platform is developed that can simultaneously enhance ROS generation while self-monitoring its levels through ratiometric photoacoustic (PA) imaging. The NP platform can further guide in vivo therapeutic effect in tumors. The theranostic NP platform is composed of: (i) cisplatin prodrug and ferric ion catalyst for ROS generation, a part of combination cancer therapy; and (ii) a ratiometric PA imaging nanoprobe consisting of inert semiconducting perylene-diimide (PDI) and ROS activatable near-infrared dye (IR790s), used in ratiometric PA imaging of ROS during cancer treatment. Ratiometric PA signals are measured at two near-infrared excitation wavelengths: 680 and 790 nm for PDI and IR790s, respectively. The measurements show highly accurate visualization of • OH generation in vivo. This novel ROS responsive organic theranostic NP allows not only synergistic cancer chemotherapy but also real-time monitoring of the therapeutic effect through ratiometric PA imaging.