用于卵巢癌化疗-光热联合治疗的吉西他滨/聚吡咯复合纳米粒子

利用铁离子诱发吡咯氧化聚合反应制备了尺寸均一的聚吡咯纳米粒子, 并进一步负载化疗药物吉西他滨, 得到了吉西他滨/聚吡咯复合纳米粒子. 该复合纳米粒子对吉西他滨的负载能力强, 在水溶液中的稳定性好, 有助于降低吉西他滨对正常组织的毒副作用. 此外, 该复合纳米粒子在近红外光区有较强的吸收, 能够将吸收的光能转化为热, 是一种良好的光热试剂, 具有光热治疗功能. 同时, 该复合纳米粒子能够在热刺激下释放吉西他滨, 具有光热介导的化疗功能. 因此, 吉西他滨/聚吡咯复合纳米粒子是一种兼具化疗和光热治疗功能的联合治疗试剂. 复合纳米粒子在808 nm近红外激光照射下能够快速提升系统温度, 实现光热治疗与化疗联合杀伤卵巢癌细胞, 具有良好的生物医学应用潜力.     

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.     

Picosecond Time Resolved Hard X-Ray Diffraction from Laser Heated Metallic Crystals

We report the development of a novel hard X-ray diffraction system with picosecond time resolution. Picosecond X-ray pulses are produced by excitation of an X-ray diode with picosecond ultraviolet light pulses at a repetition rate of 300 Hz. The X-ray pulses are synchronized to the optical pulses with picosecond accuracy. The system has been utilized in picosecond time resolved X-ray diffraction of laser pulse heated gold and platinum single crystals.     

Coherent control of the population transfer in complex solvated molecules at weak excitation. An experimental study

We performed a series of successful experiments for the optimization of the population transfer from the ground to the first excited state in a complex solvated molecule (rhodamine 101 in methanol) using shaped excitation pulses at very low intensities (1 absorbed photon per 100-500 molecules per pulse). We found that the population transfer can be controlled and significantly enhanced by applying excitation laser pulses with crafted pulse shapes. The optimal shape was found in feedback-controlled experiments using a genetic search algorithm. The temporal profile of the optimal excitation pulse corresponds to a comb of subpulses regularly spaced by approximately 150 fs, whereas its spectrum consists of a series of well-resolved peaks spaced apart by approximately 6.5 nm corresponding to a frequency of 220 cm(-1). This frequency matches very well with the frequency modulation of the population kinetics (period of approximately 150 fs), observed by excitation with a short (approximately 20 fs) transform-limited laser pulse directly after excitation. In addition, an antioptimization experiment was performed under the same conditions. The difference in the population of the excited state for the optimal and antioptimal pulses reaches approximately 30% even at very weak excitation. The results of optimization are reproducible and have clear physical meaning.     

Applications of ultrashort shaped pulses in microscopy and for controlling chemical reactions

This article presents a new perspective on laser control based on insights into the effect of spectral phase on nonlinear optical processes. Gaining this understanding requires the systematic evaluation of the molecular response as a function of a series of pre-defined accurately shaped laser pulses. The effort required is rewarded with robust, highly reproducible, results. This approach is illustrated by results on selective two-photon excitation microscopy of biological samples, where higher signal and less photobleaching damage are achieved by accurate phase measurement and elimination of high-order phase distortions from the ultrashort laser pulses. A similar systematic approach applied to laser control of gas phase chemical reactions reveals surprising general trends. Molecular fragmentation pattern is found to be dependent on phase shaping. Differently shaped pulses with similar pulse duration have been found to produce similar fragmentation patterns. This implies that any single parameter that is proportional to the pulse duration, such as second harmonic generation intensity, allows us to predict the molecular fragmentation pattern within the experimental noise. This finding, is illustrated here for a series of isomers. Bond selectivity, coherent photochemistry and their applications are discussed in light of results from these systematic studies.     

Wet-chemical synthesis and characteristics of Au nanoshell

Noble metal nanostructures have been the research focus for many decades because of their real or poten-tial applications, such as catalysis, photography, optics, electronics, optoelectronics, information storage, bio-logical and chemical sensing, surface…     

二元混合表面活性剂用于窄吸收金纳米棒的无种子合成

利用十六烷基三甲基溴化铵(CTAB)和油酸钠(NaOL)二元混合表面活性剂体系, 开发了一种高质量金纳米棒(AuNRs)的无种子合成方法. 通过透射电子显微镜(TEM)、 紫外-可见-近红外吸收光谱(UV-Vis-NIR)和热成像仪对金纳米棒的形貌、 光学性质及光热性能进行了表征. 实验结果表明, 当NaOL浓度为8.21~11.5 mmol/L时, 能够获得形貌均匀的AuNRs, 其纵向表面等离子体共振吸收(LSPR)在650~1150 nm范围内可调. 该方法制得的样品具有较窄的LSPR半峰宽, 特别是在制备LSPR在近红外二区(NIR-II, 大于1000 nm)的AuNRs方面具有明显优势. 在1064 nm激光的辐照下, 金纳米棒溶液能够快速升温至67 ℃, 光热转换效率可达31.5%, 同时表现出优秀的光热稳定性, 在近红外二区光声成像和光热治疗方面具有良好的应用价值.     

金纳米花介导的近红外热疗对人喉癌Hep-2细胞增殖的抑制作用

采用弱配体柠檬酸钠修饰的金纳米花为介导材料,考察了其对人喉癌Hep-2细胞的NIR热疗作用,结果表明,这种金纳米花材料具有良好的NIR光热转换性能,可有效抑制Hep-2细胞增殖.     

Bimodal Size Distribution of Gold Nanoparticles under Picosecond Laser Pulses

The evolution of size distributions of gold nanoparticles under pulsed laser irradiation (Nd:YAG, lambda = 355 nm, pulse width 30 ps) was carefully observed by transmission electron microscopy. Interestingly, the initial monomodal size distribution of gold nanoparticles turned into a bimodal one, with two peaks in the number of particles, one at 6 nm and the other at 16-24 nm. The sizes for small particles depended very little on the irradiated laser energy. This change is attributed to laser-induced size reduction of the initial gold nanoparticles followed by the formation of small particles. In our analysis, we extracted a characteristic value for the size-reduction rate per one pulse and revealed that laser-induced size reduction of gold nanoparticles occurred even below the boiling point. When laser energy is insufficient for the boiling of particles, formation of gold vapor around liquid gold drops is thought to cause the phenomenon. With enough laser energy for the boiling, the formation of gold vapor around and inside liquid gold drops is responsible for the phenomenon. We also observed particles with gold strings after one pulse irradiation with a laser energy of 43 mJ cm(-2) pulse(-1), which is sufficient energy for the boiling. It is considered that such particles with gold strings are formed by the projection of gaseous gold from liquid gold drops with some volume of liquid gold around the bubble. On the basis of comparison with previous work, picosecond laser pulses are thought to be the most efficient way to cause laser-induced size reduction of gold nanoparticles.     

Spectral phase effects on nonlinear resonant photochemistry of 1,3-cyclohexadiene in solution

We have investigated the ring opening of 1,3-cyclohexadiene to form 1,3,5-cis-hexatriene (Z-HT) using optical pulse shaping to enhance multiphoton excitation. A closed-loop learning algorithm was used to search for an optimal spectral phase function, with the effectiveness or fitness of each optical pulse assessed using the UV absorption spectrum. The learning algorithm was able to identify pulses that increased the formation of Z-HT by as much as a factor of 2 and to identify pulse shapes that decreased solvent fragmentation while leaving the formation of Z-HT essentially unaffected. The highest yields of Z-HT did not occur for the highest peak intensity laser pulses. Rather, negative quadratic phase was identified as an important control parameter in the formation of Z-HT.     

Controlled UV-C light-induced fusion of thiol-passivated gold nanoparticles

Thiol-passivated gold nanoparticles (AuNPs) of a relatively small size, either decorated with chromophoric groups, such as a phthalimide (Au@PH) and benzophenone (Au@BP), or capped with octadecanethiol (Au@ODCN) have been synthesized and characterized by NMR and UV-vis spectroscopy as well as transmission electron microscopy (TEM). These NPs were irradiated in chloroform at different UV-wavelengths using either a nanosecond laser (266 and 355 nm, ca. 12 mJ/pulse, 10 ns pulse) or conventional lamps (300 nm < λ < 400 nm and ca. 240 nm < λ < 280 nm) and the new AuNPs were characterized by X-ray and UV-vis spectroscopy, as well as by TEM. Laser irradiation at 355 nm led to NP aggregation and precipitation, while the NPs were photostable under UV-A lamp illumination. Remarkably, laser excitation at 266 nm induced a fast (minutes time-scale) increase in the size of the NPs, producing huge spherical nanocrystals, while lamp-irradiation at UV-C wavelengths brought about nanonetworks of partially fused NPs with a larger diameter than the native NPs.     

Noble metal coated single-walled carbon nanotubes for applications in surface enhanced Raman scattering imaging and photothermal therapy

Single-walled carbon nanotubes (SWNTs) with various unique optical properties are interesting nanoprobes widely explored in biomedical imaging and phototherapies. Herein, DNA-functionalized SWNTs are modified with noble metal (Ag or Au) nanoparticles via an in situ solution phase synthesis method comprised of seed attachment, seeded growth, and surface modification with polyethylene glycol (PEG), yielding SWNT-Ag-PEG and SWNT-Au-PEG nanocomposites stable in physiological environments. With gold or silver nanoparticles decorated on the surface, the SWNT-metal nanocomposites gain an excellent concentration and excitation-source dependent surface-enhanced Raman scattering (SERS) effect. Using a near-infrared (NIR) laser as the excitation source, targeted Raman imaging of cancer cells labeled with folic acid (FA) conjugated SWNT-Au nanocomposite (SWNT-Au-PEG-FA) is realized, with images acquired in significantly shortened periods of time as compared to that of using nonenhanced SWNT Raman probes. Owing to the strong surface plasmon resonance absorption contributed by the gold shell, the SWNTs-Au-PEG-FA nanocomposite also offers remarkably improved photothermal cancer cell killing efficacy. This work presents a facile approach to synthesize water-soluble noble metal coated SWNTs with a strong SERS effect suitable for labeling and fast Raman spectroscopic imaging of biological samples, which has been rarely realized before. The SWNT-Au-PEG nanocomposite developed here may thus be an interesting optical theranostic probe for cancer imaging and therapy.     

Influence of electronic resonances on mode selective excitation with tailored laser pulses

Femtosecond time-resolved coherent anti-Stokes Raman scattering (fs-CARS) gives access to ultrafast molecular dynamics. However, the gain of the temporal resolution entails a poor spectral resolution due to the inherent spectral width of the femtosecond excitation pulses. Modifications of the phase shape of one of the exciting pulses results in dramatic changes of the mode distribution reflected in coherent anti-Stokes Raman spectra. A feedback-controlled optimization of specific modes making use of phase and/or amplitude modulation of the pump laser pulse is applied to selectively influence the anti-Stokes signal spectrum. The optimization experiments are performed under electronically nonresonant and resonant conditions. The results are compared and the role of electronic resonances is analyzed. It can be clearly demonstrated that these resonances are of importance for a selective excitation by means of phase and amplitude modulation. The mode selective excitation under nonresonant conditions is determined mainly by the variation of the spectral phase of the laser pulse. Here, the modulation of the spectral amplitudes only has little influence on the mode ratios. In contrast to this, the phase as well as amplitude modulation contributes considerably to the control process under resonant conditions. A careful analysis of the experimental results reveals information about the mechanisms of the mode control, which partially involve molecular dynamics in the electronic states.     

Coherent control protocol for separating energy-transfer pathways in photosynthetic complexes by chiral multidimensional signals

Adaptive optimizations performed using a genetic algorithm are employed to construct optimal laser pulse configurations that separate spectroscopic features associated with the two main energy-transfer pathways in the third-order nonlinear optical response simulated for the Fenna-Matthews-Olson (FMO) photosynthetic complex from the green sulfur bacterium Chlorobium tepidum. Superpositions of chirality-induced tensor components in both collinear and noncollinear pulse configurations are analyzed. The optimal signals obtained by manipulating the ratios of various 2D spectral peaks reveal detailed information about the excitation dynamics.     

Terahertz-laser control of large amplitude vibrational motion in the sub-one-cycle pulse limit

We investigate the control of state-selective population transfer in the THz spectral range generated by sub-one-cycle pulse excitation. To this end we developed a zero-net-force modification of the optimal control algorithm which allows us to extend the algorithm into the ultrashort pulse domain. By combining the analysis of the control landscapes and that of optimal control theory, we were able to formulate a general mechanism suitable for laser control by ultrashort pulses. The strategy consists of a superposition of two pi-pulses with carrier envelope phases of phi = pi/2. The first pulse is effectively in resonance with the targeted transition, while the second one, fired at around the minimum of the first pulse second lobe, removes leaking to the dipole-coupled background state. To compensate for the pulses ultrashort duration, the carrier frequencies of both pulses are red-shifted from the spectroscopic resonance.     

Synthesis of different-sized gold nanostars for Raman bioimaging and photothermal therapy in cancer nanotheranostics

Gold nanoparticles(AuNPs) have been attractive for nanomedicine because of their pronounced optical properties.Here,we customerized the methods to synthesize two types of gold nanostars,Au nanostars-1 and Au nanostars-2,which have different spire lengths and optical properties,and also spherical AuNPs.Compared to nanospheres,gold nanostars were less toxic to a variety of cells,including macrophages.Au nanostars-1 and Au nanostars-2 also manifested a similar pattern of tissue distribution upon in vivo administration in mice to that of nanospheres,and but reveled less liver retention than nanospheres.Due to their strong absorption in the near-infrared(NIR),Au nanostars-2 induced a strong hyperthermia effect in vitro upon excitation at 808 nm,and elicited a robust photothermal therapy(PTT) efficacy in ablating tumors in a mouse model of orthotopic breast cancer using 4T1 breast cancer cells.Meanwhile,Au nanostars-1 showed a great capability to enhance the Raman signal through surface-enhanced Raman spectroscopy(SERS) in 4T1 cells.Our combined results opened a new avenue to develop Au nanostars for cancer imaging and therapy.     

Spectral quantum beating in mixed frequency/time-domain coherent multidimensional spectroscopy

Coherent multidimensional spectroscopy performed in the mixed frequency/time domain exhibits both temporal and spectral quantum beating when two quantum states are simultaneously excited. The excitation of both quantum states can occur because either the spectral width of the states or the excitation pulse exceeds the frequency separation of the quantum states. The quantum beating appears as a line that broadens and splits into two peaks and then recombines as the time delay between excitation pulses increases. The splitting depends on the spectral width of the excitation pulses. We observe the spectral quantum beating between the two nearly degenerate asymmetric carbonyl stretch modes in a nickel tricarbonyl chelate using the nonrephasing, ground state bleaching coherence pathway in triply vibrationally enhanced four-wave mixing as the time delay between the first two excitation pulses changes.     

Enhanced laser-induced breakdown spectroscopy using the combination of fourth-harmonic and fundamental Nd:YAG laser pulses

We have studied the combination of fourth-harmonic (266 nm) and fundamental (1064 nm) Nd:YAG laser pulses of the same irradiance. On a metallic target (Al), a sequence of ultraviolet (UV) and near-infrared (NIR) pulses produces deeper craters and can lead under certain conditions to analyte signal enhancements larger than those obtained with a NIR–NIR sequence. Compared to a single NIR pulse, signal enhancements by factors of approximately 30 for the Si I 288.16-nm line and 100 for the Al II 281.62-nm line were observed with double pulses of the same total energy. This effect correlates with a substantial increase in plasma temperature, with ionic lines and lines having a higher excitation energy experiencing a larger enhancement. Moreover, the optimal pulse separation is found to be larger for ionic than for neutral lines (∼3 compared to ∼0.1 μs). Another finding of this study concerns the combination of two different wavelengths (266 and 1064 nm) in a single ‘mixed-wavelength’ pulse, a scheme that also leads to an enhanced laser-induced breakdown spectroscopy (LIBS) sensitivity. It is proposed that the double-pulse and mixed-wavelength approaches are both capable of temperature and signal enhancement for the same reason: a larger portion of laser energy is absorbed in the plasma region containing the analyte atoms, instead of being absorbed at the sample surface or in the atmosphere.     

Ultrafast cooling of photoexcited electrons in gold nanoparticle-thiolated DNA conjugates involves the dissociation of the gold-thiol bond

Using UV-visible extinction spectroscopy and femtosecond pump-probe transient absorption spectroscopy, we have studied the effect of femtosecond laser heating on gold nanoparticles attached to DNA ligands via thiol groups. It is found that femtosecond pulse excitation of the DNA-modified nanoparticles at a wavelength of 400 nm leads to desorption of the thiolated DNA strands from the nanoparticle surface by the dissociation of the gold-sulfur bond. The laser-initiated gold-sulfur bond-breaking process is a new pathway for nonradiative relaxation of the optically excited electrons within the DNA-modified gold nanoparticles, as manifested by a faster decay rate of the excited electronic distribution at progressively higher laser pulse energies. The experimental results favor a bond dissociation mechanism involving the coupling between the photoexcited electrons of the nanoparticles and the gold-sulfur bond vibrations over one involving the conventional phonon-phonon thermal heating processes. The latter processes have been observed previously by our group to be effective in the selective photothermal destruction of cancer cells bound to anti-epidermal growth factor receptor-conjugated gold nanoparticles.     

The role of the laser pulse duration in infrared matrix-assisted laser desorption/ionization mass spectrometry

The role of the laser pulse duration in matrix-assisted laser desorption/ionization mass spectrometry with infrared lasers (IR-MALDI-MS) emitting in the 3 microm wavelength range has been evaluated. Mass spectrometric performance and characteristics of the IR-MALDI process were examined by comparing a wavelength-tuneable mid-infrared optical parametric oscillator (OPO) laser of 6 ns pulse duration, tuned to wavelengths of 2.79 and 2.94 microm, with an Er:YAG laser (lambda = 2.94 microm) with two pulse durations of 100 and 185 ns, and an Er:YSGG laser (lambda = 2.79 microm) with a pulse duration of 75 ns. Threshold fluences for the desorption of cytochrome C ions were determined as a function of the laser pulse duration for various common IR-MALDI matrices. For the majority of these matrices a reduction in threshold fluence by a factor of 1.2-1.9 was found by going from the 75-100 ns long pulses of the Erbium lasers to the short 6 ns OPO pulse. Within the experimental accuracy threshold fluences were equal for the 100 and the 185 ns pulse duration of the Er:YAG laser. Some pronounced pulse duration effects related to the ion formation from a glycerol matrix were also observed. The effect of the laser pulse length on the duration of ion emission was furthermore investigated.