Single-molecule photoelectron tunnelling spectroscopy.

Experimental mapping of transmission is essential for understanding and controlling charge transport through molecular devices and materials. Here we developed a single-molecule photoelectron tunnelling spectroscopy approach for mapping transmission beyond the HOMO-LUMO gap of the single diketopyrrolopyrrole molecule junction using an ultrafast-laser combined scanning tunnelling microscope-based break junction set-up at room temperature. Two resonant transport channels of ultrafast photocurrent are found by our photoelectron tunnelling spectroscopy, ranging from 1.31 eV to 1.77 eV, consistent with the LUMO + 1 and LUMO + 2 in the transmission spectrum obtained by density functional theory calculations. Moreover, we observed the modulation of resonant peaks by varying bias voltages, which demonstrates the ability to quantitatively characterize the effect of the electric field on frontier molecular orbitals. Our single-molecule photoelectron tunnelling spectroscopy offers an avenue that allows us to explore the nature of energy-dependent charge transport through single-molecule junctions.

Light-Driven Reversible Intermolecular Proton Transfer at Single-Molecule Junctions.

Photoresponsive molecular systems are essential for molecular optoelectronic devices, but most molecular building blocks are non-photoresponsive. Employed here is a photoinduced proton transfer (PIPT) strategy to control charge transport through single-molecule azulene junctions with visible light under ambient conditions, which leads to a reversible and controllable photoresponsive molecular device based on non-photoresponsive molecules and a photoacid. Also demonstrated is the application of PIPT in two single-molecule AND gate and OR gate devices with electrical signal as outputs.

Multicenter-Bond-Based Quantum Interference in Charge Transport Through Single-Molecule Carborane Junctions.

Molecular components are vital to introduce and manipulate quantum interference (QI) in charge transport through molecular electronic devices. Up to now, the functional molecular units that show QI are mostly found in conventional π- and σ-bond-based systems; it is thus intriguing to study QI in multicenter bonding systems without both π- and σ-conjugations. Now the presence of QI in multicenter-bond-based systems is demonstrated for the first time, through the single-molecule conductance investigation of carborane junctions. We find that all the three connectivities in carborane frameworks show different levels of destructive QI, which leads to highly suppressed single-molecule conductance in para- and meta-connected carboranes. The investigation of QI into carboranes provides a promising platform to fabricate molecular electronic devices based on multicenter bonds.

Plasmon-Molecule Interactions in Single-Molecule Junctions.

Single-molecule optoelectronics offers opportunities for advancing integrated photonics and electronics, which also serves as a tool to elucidate the underlying mechanism of light-matter interaction. Plasmonics, which plays pivotal role in the interaction of photons and matter, have became an emerging area. A comprehensive understanding of the plasmonic excitation and modulation mechanisms within single-molecule junctions (SMJs) lays the foundation for optoelectronic devices. Consequently, this review primarily concentrates on illuminating the fundamental principles of plasmonics within SMJs, delving into their research methods and modulation factors of plasmon-exciton. Moreover, we underscore the interaction phenomena within SMJs, including the enhancement of molecular fluorescence by plasmonics, Fano resonance and Rabi splitting caused by the interaction of plasmon-exciton. Finally, by emphasizing the potential applications of plasmonics within SMJs, such as their roles in optical tweezers, single-photon sources, super-resolution imaging, and chemical reactions, we elucidate the future prospects and current challenges in this domain.

Charge transport through single-molecule bilayer-graphene junctions with atomic thickness.

The van der Waals interactions (vdW) between π-conjugated molecules offer new opportunities for fabricating heterojunction-based devices and investigating charge transport in heterojunctions with atomic thickness. In this work, we fabricate sandwiched single-molecule bilayer-graphene junctions via vdW interactions and characterize their electrical transport properties by employing the cross-plane break junction (XPBJ) technique. The experimental results show that the cross-plane charge transport through single-molecule junctions is determined by the size and layer number of molecular graphene in these junctions. Density functional theory (DFT) calculations reveal that the charge transport through molecular graphene in these molecular junctions is sensitive to the angles between the graphene flake and peripheral mesityl groups, and those rotated groups can be used to tune the electrical conductance. This study provides new insight into cross-plane charge transport in atomically thin junctions and highlights the role of through-space interactions in vdW heterojunctions at the molecular scale.

Electrostatic gating of single-molecule junctions based on the STM-BJ technique.

The gating of charge transport through single-molecule junctions is considered a critical step towards molecular circuits but remains challenging. In this work, we report an electrostatic gating method to tune the conductance of single-molecule junctions using the scanning tunneling microscope break junction (STM-BJ) technique incorporated with a back-gated chip as a substrate. We demonstrated that the conductance varied at different applied gating voltages (Vgs). The HOMO-dominated molecules show a decrease in conductance with an increase in Vg, and the LUMO-dominated molecules show the opposite trend. The measured conductance trends with Vg are consistent with the transition voltage spectroscopy measurements. Moreover, the transmission functions simulated from density functional theory (DFT) calculations and the finite element analysis all suggest that Vg changed the energy alignment of the molecular junction. This work provides a simple method for modulating the molecular orbitals' alignment relative to the Fermi energy (Ef) of metal electrodes to explore the charge transport properties at the single-molecule scale.

Electric-Field-Induced Connectivity Switching in Single-Molecule Junctions.

The manipulation of molecule-electrode interaction is essential for the fabrication of molecular devices and determines the connectivity from electrodes to molecular components. Although the connectivity of molecular devices could be controlled by molecular design to place anchor groups in different positions of molecule backbones, the reversible switching of such connectivities remains challenging. Here, we develop an electric-field-induced strategy to switch the connectivity of single-molecule junctions reversibly, leading to the manipulation of different connectivities in the same molecular backbone. Our results offer a new concept of single-molecule manipulation and provide a feasible strategy to regulate molecule-electrode interaction.

Exploring the thermoelectric properties of oligo(phenylene-ethynylene) derivatives.

Seebeck coefficient measurements provide unique insights into the electronic structure of single-molecule junctions, which underpins their charge and heat transport properties. Since the Seebeck coefficient depends on the slope of the transmission function at the Fermi energy (EF), the sign of the thermoelectric voltage will be determined by the location of the molecular orbital levels relative to EF. Here we investigate thermoelectricity in molecular junctions formed from a series of oligophenylene-ethynylene (OPE) derivatives with biphenylene, naphthalene and anthracene cores and pyridyl or methylthio end-groups. Single-molecule conductance and thermoelectric voltage data were obtained using a home-built scanning tunneling microscope break junction technique. The results show that all the OPE derivatives studied here are dominated by the lowest unoccupied molecular orbital level. The Seebeck coefficients for these molecules follow the same trend as the energy derivatives of their corresponding transmission spectra around the Fermi level. The molecule terminated with pyridyl units has the largest Seebeck coefficient corresponding to the highest slope of the transmission function at EF. Density-functional-theory-based quantum transport calculations support the experimental results.

Modularized Tuning of Charge Transport through Highly Twisted and Localized Single-Molecule Junctions.

Although most molecular electronic devices and materials consist of a backbone with a planar structure, twisted molecular wires with reduced inter-ring π-orbital overlap offer a unique opportunity for the modularized fabrication of molecular electronic devices. Herein we investigate the modularized tuning of the charge transport through the localized molecules by designing highly twisted molecules and investigating their single-molecule charge transport using the scanning tunneling microscopy break junction technique. We find that the anthracenediyl-core molecule with a 90° inter-ring twist angle shows an unexpectedly high conductance value, which is five times higher than that of the phenylene-core molecule with a similar configuration, whereas the conductance of the delocalized planar molecule with an anthracenediyl core or a phenylene core is almost the same. Theoretical calculations revealed that highly twisted angles result in weak interactions between molecular building blocks, for which molecule orbitals are separated into localized blocks, which offers the chance for the modularized tuning of every single block. Our findings offer a new strategy for the design of future molecular devices with a localized electronic structure.

Tailored Mesoporous Silica Nanoparticles for Controlled Drug Delivery: Platform Fabrication, Targeted Delivery, and Computational Design and Analysis.

Mesoporous silica nanoparticles (MSNs) are exceptionally promising drug carriers for controlled drug delivery systems because their morphology, pore structure, pore volume and pore size can be well tailored to obtain certain drug release profiles. Moreover, they possess the ability to specifically transport and deliver anti-cancer drugs when targeting molecules are properly grafted onto their surface. MSNs based drug delivery systems have the potential to revolutionize cancer therapy. This review provides a comprehensive overview of the fabrication, modification of MSNs and their applications in tumour-targeted delivery. In addition, the characterization and analysis of MSNs with computer aided strategies were described. The existing issues and future prospective concerning the applications of MSNs as drug carriers for controlled drug delivery systems were discussed.

Overcoming acquired drug resistance in colorectal cancer cells by targeted delivery of 5-FU with EGF grafted hollow mesoporous silica nanoparticles.

Acquired drug resistance (ADR) can be developed in colorectal cancer cells after 5-fluorouracil (5-FU) treatment and diminish the effectiveness of chemotherapy. In this work, acquired 5-FU resistance in the colorectal cancer cell line SW480 was obtained with the up-regulation of dihydropyrimidine dehydrogenase (DPYD) gene expression which can convert 5-FU to its inactive metabolite. To overcome ADR in colorectal cancer, hollow mesoporous silica nanoparticles (HMSNs) grafted with epidermal growth factor (EGF) were used as nanocarriers to deliver 5-FU to colorectal cancer cells with acquired drug resistance. The effect and mechanism of 5-FU loaded EGF grafted HMSNs (EGF-HMSNs-5-FU) in overcoming acquired drug resistance in SW480/ADR cells were studied. The EGF-HMSNs were demonstrated to be specifically internalized in EGFR overexpressed SW480/ADR cells via a receptor-mediated endocytosis and can escape from endo-lysosomes. The EGF-HMSNs-5-FU exhibited much higher cytotoxicity on SW480/ADR cells than HMSNs-5-FU and free 5-FU while the plain HMSNs did not show significant cytotoxicity. The mechanism of EGF-HMSNs-5-FU in overcoming drug resistance in SW480/ADR cells could be attributed to the specific internalization of EGF-HMSNs-5-FU in EGFR overexpressed cells which can lead to high intracellular drug accumulation and cause cell death through S phase arrest.

Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles.

The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC50 of 5.69 µg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC50 of 22.9 and 14.17 µg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.

The control of epidermal growth factor grafted on mesoporous silica nanoparticles for targeted delivery.

The performance of biomaterials in a biological environment is largely influenced by the surface properties of the biomaterials. In particular, grafted targeting ligands significantly impact the subsequent cellular interactions. The utilisation of a grafted epidermal growth factor (EGF) is effective for targeted delivery of drugs to tumours, but the amount of these biological attachments cannot be easily quantified as most characterization methods could not detect the extremely low amount of EGF ligands grafted on the surface of nanoparticles. In this study, hollow mesoporous silica nanoparticles (HMSNs) were functionalized with amine groups to conjugate with EGFs via carbodiimide chemistry. Time of flight secondary ion mass spectrometry (ToF-SIMS), a very surface specific technique (penetration depth <1.5 nm), was employed to study the binding efficiency of the EGF to the nanoparticles. Principal component analysis (PCA) was implemented to track the relative surface concentrations of EGFs on HMSNs. It was found that ToF-SIMS combined with the PCA technique is an effective method to evaluate the immobilization efficiency of EGFs. Based on this useful technique, the quantity and density of the EGF attachments that grafted on nanoparticles can be effectively controlled by varying the EGF concentration at grafting stages. Cell experiments demonstrated that the targeting performance of EGFR positive cells was affected by the number of EGFs attached on HMSNs.

Fabrication of high specificity hollow mesoporous silica nanoparticles assisted by Eudragit for targeted drug delivery.

Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising carriers for effective drug delivery due to their large surface area, high volume for drug loading and excellent biocompatibility. However, the non-ionic surfactant templated HMSNs often have a broad size distribution and a defective mesoporous structure because of the difficulties involved in controlling the formation and organization of micelles for the growth of silica framework. In this paper, a novel "Eudragit assisted" strategy has been developed to fabricate HMSNs by utilising the Eudragit nanoparticles as cores and to assist in the self-assembly of micelle organisation. Highly dispersed mesoporous silica spheres with intact hollow interiors and through pores on the shell were fabricated. The HMSNs have a high surface area (670 m(2)/g), small diameter (120 nm) and uniform pore size (2.5 nm) that facilitated the effective encapsulation of 5-fluorouracil within HMSNs, achieving a high loading capacity of 194.5 mg(5-FU)/g(HMSNs). The HMSNs were non-cytotoxic to colorectal cancer cells SW480 and can be bioconjugated with Epidermal Growth Factor (EGF) for efficient and specific cell internalization. The high specificity and excellent targeting performance of EGF grafted HMSNs have demonstrated that they can become potential intracellular drug delivery vehicles for colorectal cancers via EGF-EGFR interaction.

EpCAM Aptamer-mediated Survivin Silencing Sensitized Cancer Stem Cells to Doxorubicin in a Breast Cancer Model.

Understanding the molecular basis of drug resistance and utilising this information to overcome chemoresistance remains a key challenge in oncology. Here we report that survivin, a key protein implicated in drug resistance, is overexpressed in cancer stem cell pool of doxorubicin-resistant breast cancer cells. Moreover, by utilising an active targeting system consisting of an RNA aptamer targeted against the epithelial cell adhesion molecule and a Dicer substrate survivin siRNA, we could deliver a high dose of the siRNA to cancer stem cells in xenograft tumours. Importantly, silencing of survivin with this aptamer-siRNA chimera in cancer stem cell population led to the reversal of chemoresistance, such that combined treatment with low dose of doxorubicin inhibited stemness, eliminated cancer stem cells via apoptosis, suppressed tumour growth, and prolonged survival in mice bearing chemoresistant tumours. This strategy for in vivo cancer stem cell targeting has wide application for future effective silencing of anti-death genes and in fact any dysregulated genes involved in chemoresistance and tumour relapse.

Effects of Chinese Materia Medica-Fubao Danggui Jiao on experimental endometriosis.

The objective of this paper was to investigate the effects of a Chinese Materia Medica variant -Fubao Danggui Jiao (FDJ)-on experimental endometriosis. An endometriosis model was created by virtue of auto-transplantation of endometrial tissue onto rats' abdominal walls. The implants were allowed to grow for 30 days until the successful completion of the model. After that, forty endometriotic rats were randomly divided into four study groups and given different treatments: (1) negative control group (water, 2ml/kg, per os); (2) FDJ-A group (FDJ, 2ml/kg, per os); (3) FDJ-B group (FDJ, 4ml/kg, per os); (4) Danazol group (70mg/kg, per os). After 30 days with treatments, the volumes of endometriotic implants in each rat were measured. The implants and normal uterine horns were removed for routine histological examination. FDJ caused significant decreases in volumes of the surviving endometriotic implants, with two different doses having statistically equivalent effects. Upon histological examination, FDJ was observed to cause regression of epithelium and stroma of endometriotic implants. FDJ had revealed promising therapeutic effects on endometriosis.

Synthesis and characterization of folate conjugated chitosan and cellular uptake of its nanoparticles in HT-29 cells.

Folate-chitosan (FA-CS) conjugates synthesized by coupling FA with CS render new and improved functions because the original properties of CS are maintained and the targeting ligand of FA is incorporated. In this work, FA-CS conjugates were synthesized based on chemical linking of carboxylic group of FA with amino group of CS as confirmed by Fourier transform spectroscopy (FTIR) and nuclear magnetic resonance ((1)H NMR). FA-CS conjugates displayed less crystal nature when compared to CS. The FA-CS nanoparticles (NPs) were prepared by crosslinking FA-CS conjugates with sodium tripolyphosphate (STPP). Positively charged FA-CS nanoparticles were spherical in shape with a particle size of about 100 nm. Cellular uptake of CS or FA-CS nanoparticles was assayed by fluorescent microscopy using calcein as fluorescent marker in colon cancer cells (HT-29). The FA-CS nanoparticles exhibited improved uptake of HT-29 and could become a potential targeted drug delivery system for colorectal cancer.