PAA-derived gold nanorods for cellular targeting and photothermal therapy

A single-step LbL procedure to functionalize CTAB-capped GNRs via electrostatic self-assembly is reported. This approach allows for consistent biomolecule/GNR coupling using standard carboxyl-amine conjugation chemistry. The focus is on cancer-targeting biomolecule/GNR conjugates and selective photothermal destruction of cancer cells by GNR-mediated hyperthermia and NIR light. GNRs were conjugated to a single-chain antibody selective for colorectal carcinoma cells and used as probes to demonstrate photothermal therapy. Selective targeting and GNR uptake in antigen-expressing SW 1222 cells were observed using fluorescence microscopy. Selective photothermal therapy is demonstrated using SW 1222 cells, where >62% cell death was observed after cells are treated with targeted A33scFv-GNRs.     

Gold Nanorod–Photosensitizer Complex Obtained by Layer‐by‐Layer Method for Photodynamic/Photothermal Therapy In Vitro

Gold nanorod (GNR)–photosensitizer (PS) complex was prepared using anionic PS (sodium salt of purpurin‐18) and cationic poly(allylamine hydrochloride) by layer‐by‐layer method, and was characterized by transmission electron microscopy, UV‐vis spectroscopy, and zeta potential. The GNR–PS complex is a promising agent for synergistic (photothermal and photodynamic) therapy (PTT/PDT), in which PTT generates heat as well as operates the PS release which maximize the following PDT activity. The combined dual therapy, PTT followed by PDT, exhibits a significantly higher photocytotoxicity result based on synergistic effect of hyperthermia from PTT as well as singlet oxygen photogeneration from PDT.     

适体功能化的金纳米棒用于癌症靶向治疗的研究进展

金纳米棒(gold nanorods,GNRs)具有特殊的光学性质、较大的比表面积、出色的光热转换性能、表面易修饰等特点,在药物递送、光疗、生物成像和化学传感等领域应用十分广泛。适体是短的单链DNA或RNA片段,可特异性识别癌细胞或其表面的膜蛋白。近年来,适体功能化的GNRs在癌症靶向治疗领域显示出良好的应用前景。根据GNRs对癌症作用机制的差异,本文从光热疗法、光动力疗法、化疗和联合疗法4个方面总结了适体功能化的GNRs在癌症靶向治疗中的最新进展,并对该领域面临的主要挑战和发展趋势进行了探讨与展望。     

A Supramolecular-Based Dual-Wavelength Phototherapeutic Agent with Broad-Spectrum Antimicrobial Activity Against Drug-Resistant Bacteria

With the ever-increasing threat posed by the multi-drug resistance of bacteria, the development of non-antibiotic agents for the broad-spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supramolecular self-assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one-dimensional wire-like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual-modal properties with significant reactive-oxygen-species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram-positive, Gram-negative, and drug-resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual-modal antimicrobial agents that are able to overcome antibiotic resistance.     

A Supramolecular‐Based Dual‐Wavelength Phototherapeutic Agent with Broad‐Spectrum Antimicrobial Activity Against Drug‐Resistant Bacteria

With the ever‐increasing threat posed by the multi‐drug resistance of bacteria, the development of non‐antibiotic agents for the broad‐spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supramolecular self‐assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one‐dimensional wire‐like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual‐modal properties with significant reactive‐oxygen‐species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram‐positive, Gram‐negative, and drug‐resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual‐modal antimicrobial agents that are able to overcome antibiotic resistance.     

Supramolecular Nanostructures of Structurally Defined Graphene Nanoribbons in the Aqueous Phase

Structurally well‐defined graphene nanoribbons (GNRs) have attracted great interest because of their unique optical, electronic, and magnetic properties. However, strong π–π interactions within GNRs result in poor liquid‐phase dispersibility, which impedes further investigation of these materials in numerous research areas, including supramolecular self‐assembly. Structurally defined GNRs were synthesized by a bottom‐up strategy, involving grafting of hydrophilic poly(ethylene oxide) (PEO) chains of different lengths (GNR‐PEO). PEO grafting of 42–51 % percent produces GNR‐PEO materials with excellent dispersibility in water with high GNR concentrations of up to 0.5 mg mL^?1. The “rod–coil” brush‐like architecture of GNR‐PEO resulted in 1D hierarchical self‐assembly behavior in the aqueous phase, leading to the formation of ultralong nanobelts, or spring‐like helices, with tunable mean diameters and pitches. In aqueous dispersions the superstructures absorbed in the near‐infrared range, which enabled highly efficient conversion of photon energy into thermal energy.     

Selective photothermal therapy for breast cancer with targeting peptide modified gold nanorods

In this work, we prepared polyacrylic acid (PAA) coated gold nanorods (GNRs) and then the targeting peptide modified GNRs. The biocompatibility and stability of functionalized GNRs were investigated by monitoring the surface plasmon resonance (SPR) absorption intensity. The efficacy of targeted thermal therapy can be significantly enhanced via decoration with surface-bound peptide which was obtained through phage display technology. In addition, the photothermal therapy was monitored in real time with the multi-channel function of a confocal laser scanning microscope (CLSM) coupled with an 808 nm laser. This selective photothermal therapy of GNRs is a promising candidate for phototherapeutic applications.     

Study of Electronic,Optical Absorption and Emission in Pure and Metal‐Decorated Graphene Nanoribbons (C29H14‐X; X=Ni,Fe, Ti,Co+, Al+, Cu+): First Principles Calculations

Density functional theory (DFT) and time‐dependent density functional theory (TDDFT) calculations were performed with the basis sets 6‐31G for DFT and 6‐31G(d), 6‐31+G(d,p) for TDDFT on pure graphene nanoribbon (GNR) C₃₀H₁₄ and metal‐decorated C₂₉H₁₄‐X (MGNRs; X=Ni, Fe, Ti, Co⁺, Al⁺, and Cu⁺). The metal/carbon ratio (X:C 3.45 %) and the doping site were fixed. Electronic properties, that is, the dipole moment, binding energy, and HOMO–LUMO gaps, were calculated. The absorption and emission properties in the visible range (λ=400–720 nm) were determined. Optical gaps, absorption and emission wavelengths, oscillator strengths, and dominant transitions were calculated. Pure graphene was found to be the most stable form. However, of the MGNRs, C₂₉H₁₄?Co⁺ and C₂₉H₁₄?Al⁺ were found to be the most and least stable, respectively. All GNRs were found to have semiconducting nature. The optical absorption of pure graphene undergoes a shift on metal doping. Emission from the pure graphene followed Kasha′s rule, unlike the metal‐doped GNRs.     

Gold nanorod separation and characterization by asymmetric-flow field flow fractionation with UV–Vis detection

The application of asymmetric-flow field flow fractionation (A4F) for low aspect ratio gold nanorod (GNR) fractionation and characterization was comprehensively investigated. We report on two novel aspects of this application. The first addresses the analytical challenge involved in the fractionation of positively charged nanoparticles by A4F, due to the interaction that exists between the negatively charged native membrane and the analyte. We show that the mobile phase composition is a critical parameter for controlling fractionation and mitigating the membrane-analyte interaction. A mixture of ammonium nitrate and cetyl trimethyl ammonium bromide at different molar ratios enables separation of GNRs with high recovery. The second aspect is the demonstration of shape-based separation of GNRs in A4F normal mode elution (i.e., Brownian mode). We show that the elution of GNRs is due both to aspect ratio and a steric-entropic contribution for GNRs with the same diameter. This latter effect can be explained by their orientation vector inside the A4F channel. Our experimental results demonstrate the relevance of the theory described by Beckett and Giddings for non-spherical fractionation (Beckett and Giddings, J Colloid and Interface Sci 186(1):53–59, 1997). However, it is shown that this theory has its limit in the case of complex GNR mixtures, and that shape (i.e., aspect ratio) is the principal material parameter controlling elution of GNRs in A4F; the apparent translational diffusion coefficient of GNRs increases with aspect ratio. Finally, the performance of the methodology developed in this work is evaluated by the fractionation and characterization of individual components from a mixture of GNR aspect ratios.     

Biomimetic Synthesis of Ag2Se Quantum Dots with Enhanced Photothermal Properties and as “Gatekeepers” to Cap Mesoporous Silica Nanoparticles for Chemo–Photothermal Therapy

Ag₂Se quantum dots (QDs) with near‐infrared (NIR) fluorescence have been widely utilized in NIR fluorescence imaging in vivo because of their narrow bulk band gap and excellent biocompatibility. However, most of synthesis methods for Ag₂Se QDs are expensive and the reactants are toxic. Herein, a new protein‐templated biomimetic synthesis approach is proposed for the preparation of Ag₂Se QDs by employing bovine serum albumin (BSA) as a template and dispersant. The BSA‐templated Ag₂Se QDs (Ag₂Se@BSA QDs) showed NIR fluorescence with high fluorescence quantum yield (≈21.2 %), excellent biocompatibility and good dispersibility in different media. Moreover, the obtained Ag₂Se@BSA QDs exhibited remarkable photothermal conversion (≈27.8 %), which could be used in photothermal therapy. As a model application in biomedicine, the Ag₂Se@BSA QDs were used as “gatekeepers” to cap mesoporous silica nanoparticles (MSNs) by means of electrostatic interaction. By taking the advantages of NIR fluorescence and photothermal property of Ag₂Se@BSA QDs, the obtained MSN‐DOX‐Ag₂Se nanoparticles (MDA NPs) were employed as a nanoplatform for combined chemo‐photothermal therapy. Compared with free DOX and MDA NPs without NIR laser, the laser‐treated MDA NPs exhibited lower cell viability in vitro, implying that Ag₂Se@BSA QDs are highly promising photothermal agents and the MDA NPs are potential carriers for chemo–photothermal therapy.     

Optimizing the formation of biocompatible gold nanorods for cancer research: functionalization, stabilization and purification

We have investigated the most efficient way of preparing biocompatible gold nanorods (GNR) used as tool for cancer imaging and therapy. The surface of cetyltrimethylammonium bromide-stabilized gold nanorods (GNR-CTAB) was functionalized with various thio-polyethylene glycols of the general formula HS-PEGmX (m=356-10,000; X=-OMe, -NH(2)). The influence of several parameters such as PEG chain length, reaction conditions and purification method on long-term stability, morphology and optical properties of the produced GNR-S-PEGmX was studied, demonstrating the existence of a threshold HS-PEGmX chain length (with molecular weight m≥2000) for efficient steric stabilization of GNR. Several purification techniques were compared: dialysis, centrifugation and a rarely used technique in this field, size exclusion chromatography. While a very weak efficiency of dialysis was evidenced, both centrifugation and size exclusion chromatography were found to provide pure GNRs, though the latter method yielded nanoparticles with a significantly higher stability. Finally, the long-term stability of the produced GNRs was investigated in various media: water, PBS buffer and serum.     

On-surface synthesis of singly and doubly porphyrin-capped graphene nanoribbon segments

On-surface synthesis has emerged as a powerful tool for the construction of large, planar, π-conjugated structures that are not accessible through standard solution chemistry. Among such solid-supported architectures, graphene nanoribbons (GNRs) hold a prime position for their implementation in nanoelectronics due to their manifold outstanding properties. Moreover, using appropriately designed molecular precursors, this approach allows the synthesis of functionalized GNRs, leading to nanostructured hybrids with superior physicochemical properties. Among the potential “partners” for GNRs, porphyrins (Pors) outstand due to their rich chemistry, robustness, and electronic richness, among others. However, the use of such π-conjugated macrocycles for the construction of GNR hybrids is challenging and examples are scarce. Herein, singly and doubly Por-capped GNR segments presenting a commensurate and triply-fused GNR–Por heterojunction are reported. The study of the electronic properties of such hybrid structures by high-resolution scanning tunneling microscopy, scanning tunneling spectroscopy, and DFT calculations reveals a weak hybridization of the electronic states of the GNR segment and the Por moieties despite their high degree of conjugation.

Singly and doubly porphyrin-capped graphene nanoribbon segments are reported and their electronic properties are studied by high-resolution scanning tunneling microscopy and spectroscopy, and DFT calculations.     

On-Surface Synthesis and Characterization of Triply Fused Porphyrin–Graphene Nanoribbon Hybrids

On-surface synthesis offers a versatile approach to prepare novel carbon-based nanostructures that cannot be obtained by conventional solution chemistry. Graphene nanoribbons (GNRs) have potential for a variety of applications. A key issue for their application in molecular electronics is in the fine-tuning of their electronic properties through structural modifications, such as heteroatom doping or the incorporation of non-benzenoid rings. In this context, the covalent fusion of GNRs and porphyrins (Pors) is a highly appealing strategy. Herein we present the selective on-surface synthesis of a Por–GNR hybrid, which consists of two Pors connected by a short GNR segment. The atomically precise structure of the Por–GNR hybrid has been characterized by bond-resolved scanning tunneling microscopy (STM) and noncontact atomic force microscopy (nc-AFM). The electronic properties have been investigated by scanning tunneling spectroscopy (STS), in combination with DFT calculations, which reveals a low electronic gap of 0.4 eV.     

Wrinkle engineering: a new approach to massive graphene nanoribbon arrays

Wrinkles are often formed on CVD-graphene in an uncontrollable way. By designing the surface morphology of growth substrate together with a suitable transfer technique, we are able to engineer the dimension, density, and orientation of wrinkles on transferred CVD-graphene. Such kind of wrinkle engineering is employed to fabricate highly aligned graphene nanoribbon (GNR) arrays by self-masked plasma-etching. Strictly consistent with the designed wrinkles, the density of GNR arrays varied from ～0.5 to 5 GNRs/μm, and over 88% GNRs are less than 10 nm in width. Electrical transport measurements of these GNR-based FETs exhibit an on/off ratio of ～30, suggesting an opened bandgap. Our wrinkle engineering approach allows very easily for a massive production of GNR arrays with bandgap-required widths, which opens a practical pathway for large-scale integrated graphene devices.     

On‐Surface Synthesis and Characterization of Triply Fused Porphyrin–Graphene Nanoribbon Hybrids

On‐surface synthesis offers a versatile approach to prepare novel carbon‐based nanostructures that cannot be obtained by conventional solution chemistry. Graphene nanoribbons (GNRs) have potential for a variety of applications. A key issue for their application in molecular electronics is in the fine‐tuning of their electronic properties through structural modifications, such as heteroatom doping or the incorporation of non‐benzenoid rings. In this context, the covalent fusion of GNRs and porphyrins (Pors) is a highly appealing strategy. Herein we present the selective on‐surface synthesis of a Por–GNR hybrid, which consists of two Pors connected by a short GNR segment. The atomically precise structure of the Por–GNR hybrid has been characterized by bond‐resolved scanning tunneling microscopy (STM) and noncontact atomic force microscopy (nc‐AFM). The electronic properties have been investigated by scanning tunneling spectroscopy (STS), in combination with DFT calculations, which reveals a low electronic gap of 0.4 eV.     

Synthesis of a Near‐Infrared BODIPY Dye for Bioimaging and Photothermal Therapy

The development of robust photothermal agents for near‐infrared (NIR) imaging is a great challenge. Herein, we report the design and synthesis of a new photothermal agent, based on the aza‐boron‐dipyrromethene framework (azaBDP). This compound possessed excellent photostability and high photothermal‐conversion efficiency (50 %) under NIR laser irradiation. When the photothermal properties of this compound were utilized for tumor inhibition, stable long‐term fluorescence was observed in living animals. Photothermal treatment efficiently suppressed tumor growth, as evidenced by in vitro and in vivo experiments. Furthermore, NIR emission could be detected by using an imaging system and therapeutic self‐monitoring was achieved by using NIR imaging.     

Red antenna states of photosystem I from cyanobacteria Synechocystis PCC 6803 and Thermosynechococcus elongatus: single-complex spectroscopy and spectral hole-burning study

Hole-burning and single photosynthetic complex spectroscopy were used to study the excitonic structure and excitation energy-transfer processes of cyanobacterial trimeric Photosystem I (PS I) complexes from Synechocystis PCC 6803 and Thermosynechococcus elongatus at low temperatures. It was shown that individual PS I complexes of Synechocystis PCC 6803 (which have two red antenna states, i.e., C706 and C714) reveal only a broad structureless fluorescence band with a maximum near 720 nm, indicating strong electron-phonon coupling for the lowest energy C714 red state. The absence of zero-phonon lines (ZPLs) belonging to the C706 red state in the emission spectra of individual PS I complexes from Synechocystis PCC 6803 suggests that the C706 and C714 red antenna states of Synechocystis PCC 6803 are connected by efficient energy transfer with a characteristic transfer time of approximately 5 ps. This finding is in agreement with spectral hole-burning data obtained for bulk samples of Synechocystis PCC 6803. The importance of comparing the results of ensemble (spectral hole burning) and single-complex measurements was demonstrated. The presence of narrow ZPLs near 710 nm in addition to the broad fluorescence band at approximately 730 nm in Thermosynechococcus elongatus (Jelezko et al. J. Phys. Chem. B 2000, 104, 8093-8096) has been confirmed. We also demonstrate that high-quality samples obtained by dissolving crystals of PS I of Thermosynechococcus elongatus exhibit stronger absorption in the red antenna region than any samples studied so far by us and other groups.     

Coherent Anti‐Stokes Emission from Gold Nanorods and its Potential for Imaging Applications

We used coherent anti‐Stokes scattering (CAS) to characterize individual gold nanorods (GNRs) and GNR aggregates. By creating samples with different densities of GNRs on silicon wafer substrates, we were able to determine surface coverage by scanning electron microscopy (SEM) and then correlate the coverage to the CAS intensities of the samples. The observed CAS signal intensity was quadratically dependent on the number of particles. We also examined the CAS signal as a function of the excitation polarization and found that the strongest signals in regularly oriented GNRs were observed when the beam polarization was aligned with the longitudinal axis of the GNRs. Irregularly oriented GNRs exhibited a different scattering pattern to that observed for regularly oriented GNRs. The polarization‐dependent scattering from oriented GNRs showed cos⁶ (θ) behavior. By imaging nanoscale‐sized GNR patterns using CAS and evaluating the results with SEM, we show that CAS can be used for efficient, label‐free imaging of nanoscale metallic particles.     

基于共轭聚合物的纳米粒子用于肿瘤的近红外二区荧光成像及光热治疗

为提高生物组织荧光成像质量以及对肿瘤的高效光热治疗,设计合成了一种新型的窄带隙共轭聚合物(BDT-TTQ),并通过纳米沉积的方式将聚合物制备成水溶性纳米粒子(BDT-TTQ NPs).该共轭聚合物纳米粒子在1000~1200 nm近红外二区范围具有较好的吸收,在1064 nm的激发光下能实现1200~1400 nm的近红外二区荧光成像. BDT-TTQ NPs纳米粒子粒径分布较窄,形貌呈规则的球形且分散均匀,具有好的生物相容性.该纳米粒子既可以在体外实现较高的近红外二区荧光成像穿透深度,又可以实现对小鼠活体血管的高清晰度的近红外二区荧光成像.此外,BDT-TTQ NPs纳米粒子在1064 nm激光下展现出优异的光热转换效率,具有较高的光毒性,对体外的肿瘤细胞以及小鼠的异质瘤具有高的光热杀伤能力.     

Multispectral Plasmon of Anisotropic Core-shell Gold Nanorods@SiO2: Dual-band Absorption Enhancement with Coupling Dye Molecules

Direct evidence of effects of surface plasmon resonance(SPR) of gold nanorods(GNRs) on dual-band light absorption enhancement with coupling dye molecules was reported by introducing gold nanorod@SiO₂(GNR@SiO₂) core-shell nanoparticles into a photoelectric conversion system. GNR with asymmetric shape had unusual anisotropic SPR[transversal surface plasmon resonance(TSPR) and longitudinal surface plasmon resonance(LSPR)]. The excellent SPR of GNR made it a promising candidate as enhancing light absorption material to increase power conversion efficiency(PCE). The PCE was improved nearly 17.2% upon incorporating GNRs, mostly due to the increase in J_sc, while V_oc and FF were unchanged. The improvement was mostly contributed by the SPR of the GNRs with coupling of N719. And there was also a complementary to N719 in visible light range. Therefore, SPR is an effective tool in improving the photocurrent and consequently enhancement of PCE. The TSPR and LSPR effects of GNRs on light harvesting were reflected in the increased monochromatic incident photon-to-electron conversion efficiency(IPCE). We also utilized finite-difference time-domain(FDTD) to investigate the light coupling of GNRs with TiO₂. Compare to the base anode, the IPCE of optimized electrode showed significant improvement and peaks broadening at 500-600 nm and 610-710 nm. We got an increase in overall conversion efficiency from 6.4% to 7.5%.