Water-Soluble Conjugates of ZnS:Mn Quantum Dots with Chlorin e6 for Photodynamic Therapy

An algorithm for wavefront calculation of ordinary and extraordinary waves after propagation through hemispherical components made of a uniaxial crystal is developed. The influence of frequency dispersion of n _о and n _e , as well as change in the direction of the optic axis of the crystal, on extraordinary wavefront in hemispheres made of from leuco-sapphire and a plastically deformed analog thereof is determined.     

Formation of an Equilibrium Complex of Lactate Dehydrogenase with Chlorin e 6

Using spectrophotometric, spectral-luminescent, and polarization methods, we have detected the formation of strong equilibrium complexes of a key glycolytic enzyme — lactate dehydrogenase — with a promising photodynamic sensitizer — chlorin e ₆. It has been established that enzymes serve as the most sensitive targets destroying tumor cells subjected to photodynamic therapy.     

Regularities of Bonding of Chlorin e 6 to the Oligomeric Enzyme Lactate Dehydrogenase

Using differential-spectrophotometry, spectral-luminescence, and polarization methods, we have investigated regularities of complexing of a promising photodynamic sensitizer — chlorin e ₆ — with a key glycolytic enzyme — lactate dehydrogenase (LDH). The parameters of the dye–enzyme complex have been estimated by the difference between the spectral characteristics of the free dye and the dye bonded to the enzyme. It is shown that the tetrameric LDH molecule forms an equilibrium complex with four chlorin molecules and the sensitizer is bonded independently to each subunit entering into the composition of the tetramer. It has been established that the spectral characteristics of chlorin bonded to LDH are sensitive to the structure transformations arising in the active center of the enzyme as a result of the formation of an unproductive enzyme–coenzyme–substrate complex, which allows the conclusion that the dye is localized in the neighborhood of the active center of LDH.     

Deep-ultraviolet and visible dual-band photodetectors by integrating Chlorin e6 with Ga_2O_3

Gallium oxide(Ga_2O_3) is a promising material for deep-ultraviolet(DUV) detection. In this work, Chlorin e6(Ce6)has been integrated with Ga_2O_3 to achieve a DUV and visible dual-band photodetector, which can achieve multiple target information and improve the recognition rate. The photodetector shows two separate response bands at 268 nm and 456 nm.The DUV response band has a responsivity of 9.63 A/W with a full width at half maximum(FWHM) of 54.5 nm; the visible response band has a responsivity of 1.17 A/W with an FWHM of 45.3 nm. This work may provide a simple way to design and fabricate photodetectors with dual-band response.     

Photodynamic Therapy for Cancer Cells Using Metal-Halide Lamps

New metal-halide lamps were developed and their effect on the efficiency of photodynamic therapy (PDT) for cancer cells, murine thymic lymphoma cells (EL-4), was investigated. 5-Aminolevulinic acid-induced protoporphyrin IX was used as a photosensitizer. The metal-halide lamps were made by introducing sodium iodide (Na lamp), lithium iodide (Li lamp), and sodium iodide-lithium iodide mixture (Na-Li lamp) into their discharge tubes. These lamps emitted light in the range of 550 to 750 nm and had specific emission peaks at 580 and 600 nm for the Na lamp, 580, 610, and 680 nm for the Li lamp, and 580, 610, and 675 nm for the Na-Li lamp. Changes in the survival rate of EL-4 with increasing irradiation time indicated that PDT efficiency of the lamps increased in the order Li lamp < Na lamp < Na-Li lamp. We also found that a dark interval during irradiation of the light with the Na-Li lamp enhanced PDT efficiency.     

Elucidation of Monomerization Effect of PVP on Chlorin e6 Aggregates by Spectroscopic, Chemometric, Thermodynamic and Molecular Simulation Studies

Molecular aggregation in aqueous media is one of the factors which largely affects the efficacy of photosensitizers in photodynamic therapy. Chlorin e6 (Ce6) in aggregated form is known to exhibit markedly reduced therapeutic effects. In the present study, aggregate to monomer conversion of Ce6 was investigated as a function of pH and polyvinylpyrrolidone (PVP) concentration by simple absorption and fluorescence spectroscopic techniques. Aggregation of Ce6 was observed in the pH range of 2 to 6 as indicated by changes in UV–vis absorption spectra, fluorescence emission spectra and relative quantum yield. Novel chemometric approach was considered for determining the relative monomerization efficiency of different grades of PVP. The chemometric analysis and binding constant study both strongly revealed that the Ce6-PVP complex was more efficiently formed with PVP of the lowest molecular weight (K17). Thermodynamic parameters, such as the heat of entropy and enthalpy, showed that complex formation was largely attributed to hydrophobic interaction between Ce6 and PVP. This was found to be consistent with the results obtained from molecular simulation study.     

光动力学疗法新型光敏剂的光谱特性研究

实验研究了用于光动力学诊断和治疗的新型光敏剂二磺基二邻苯二甲酰亚胺甲基酞菁锌（ZnPcS2P)癌光啉（PsD-007)、血啉甲醚（HMME）以及早期应用于临床的血卟啉衍生物（HpD)分别在生理盐水和含10％人血清生理盐水中的光谱特性。结果表明：除ZnPcS2P2的最大吸收峰位于670nm之外，其余三种光敏剂在人血清环境中的最大吸收峰都位于405nm处，但与生理盐水环境相比索瑞（Soret)峰发生了12nm的红移。在波长为413和514.5nm光源激发下，HMME，HpD和PsD-007在人血清环境中的荧光发射峰都分别位于625和690nm，但413nm光源的激发效率比514.5nm光源高出3倍左右，而且HEEM的荧光激发效率最高，HpD次之，PsD-007最低。     

Encapsulation of Photosensitizers and Upconversion Nanocrystals in Lipid Micelles for Photodynamic Therapy

Photodynamic therapy (PDT) is a promising method for cancer therapy. However, it is constrained by limited penetration depth of visible light, hydrophobicity of photosensitizers, and lack of tumor targeting. In this work, the photosensitizer zinc phthalocyanine (ZnPc) and upconversion nanocrystals (UCNs) are encapsulated into OQPGA‐PEG/RGD/TAT lipid micelles. The UCNs acting as a nanotransducer convert deep‐penetrating near‐infrared (NIR) light to visible light for activating the photosensitizer. OQPGA‐PEG/RGD/TAT lipid micelles are used as a carrier for the photosensitizer, with improved biocompatibility and cancer‐targeting ability. The results show that the photosensitizer ZnPc‐ and UCNs‐loaded OQPGA‐PEG/RGD/TAT lipid micelles are nanoparticles with an average size of 25 nm. The lipid micelle nanoparticles are stable in water with low leakage of photosensitizer. The absorption peak of the photosensitizer overlaps with the emission peak of UCNs, so the visible fluorescence emitted from the UCNs upon excitation by the NIR laser at 980 nm can activate the photosensitizer to produce singlet oxygen for PDT. The targeting RGD peptide and cell‐penetrating TAT peptide on the surface help the nanoparticles getting into cancer cells. The OQPGA‐PEG/RGD/TAT lipid micelles encapsulated with both the photosensitizer ZnPc and UCNs could be used for targeted PDT by using deep‐penetrating NIR light as the light source.     

新型光动力学疗法光敏剂5-ALA-GNPs的制备及其光谱分析

通过聚二烯丙基二甲基胺盐酸盐和氯金酸制备阳离子纳米金,将纳米金和5-氨基乙酰丙酸(5-aminolevulinic acid, 5-ALA)通过静电吸附作用有效结合得到新型光敏剂。应用共振瑞利散射光谱, 紫外-可见吸收光谱, 透射电镜和激光散射等方法对其进行了表征。结果表明通过这种方法纳米金与5-ALA可以有效结合。这种新型光敏剂对提高光动力学疗法临床疗效具有重要指导意义。     

Photothermal/Photodynamic Therapy with Immune‐Adjuvant Liposomal Complexes for Effective Gastric Cancer Therapy

A diagnosis and therapeutic strategy for gastric cancer is developed herein by combining thermosensitive liposomal (TSL)‐based photothermal/photodynamics therapy (PTT/PDT) with chemotherapy and adjuvant immunotherapy. IR820, a photothermal agent, paclitaxel (PTX), an antitumor drug, and imiquimod (R837), a Toll‐like‐receptor‐7 agonist, are coencapsulated into a TSL drug delivery system. These formed PTX‐R837‐IR820@TSL complexes exhibit excellent optical properties, good dispersibility, and stability. Under NIR light irradiation, the measurement of singlet oxygen production and thermal efficiency indicate promising potential of PTX‐R837‐IR820@TSL complexes for PTT and PDT. Confocal microscopy and small animal NIR imaging demonstrate tumor targeting ability of the liposomal complexes to gastric cancer cells. In vitro cell viability assays and in vivo animal experiments show prominent antitumor efficiency of PTX‐R837‐IR820@TSL complexes upon NIR light irradiation. This excellent therapeutic efficacy is attributed to the simultaneous chemotherapy and PTT/PDT. Furthermore, the liposomal complexes under NIR irradiation would ablate tumors to generate a pool of tumor‐associated antigens, which is able to promote strong antitumor immune responses in the presence of those R837‐containing liposomal complexes acted as adjuvant. These results indicate that the multifunctional liposomal complexes could realize a remarkable synergistic therapeutic outcome in gastric carcinoma.     

Peptide‐Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer

Targeted drug delivery using epidermal growth factor peptide‐targeted gold nanoparticles (EGF_pep‐Au NPs) is investigated as a novel approach for delivery of photodynamic therapy (PDT) agents, specifically Pc 4, to cancer. In vitro studies of PDT show that EGF_pep‐Au NP‐Pc 4 is twofold better at killing tumor cells than free Pc 4 after increasing localization in early endosomes. In vivo studies show that targeting with EGF_pep‐Au NP‐Pc 4 improves accumulation of fluorescence of Pc 4 in subcutaneous tumors by greater than threefold compared with untargeted Au NPs. Targeted drug delivery and treatment success can be imaged via the intrinsic fluorescence of the PDT drug Pc 4. Using Pc 4 fluorescence, it is demonstrated in vivo that EGF_pep‐Au NP‐Pc 4 impacts biodistribution of the NPs by decreasing the initial uptake by the reticuloendothelial system (RES) and by increasing the amount of Au NPs circulating in the blood 4 h after IV injection. Interestingly, in vivo PDT with EGF_pep‐Au NP‐Pc 4 results in interrupted tumor growth when compared with EGF_pep‐Au NP control mice when selectively activated with light. These data demonstrate that EGF_pep‐Au NP‐Pc 4 utilizes cancer‐specific biomarkers to improve drug delivery and therapeutic efficacy over untargeted drug delivery.     

Photodynamic Therapy for Cancer Cells Using a Flash Wave Light Xenon Lamp

We determined photodynamic therapy (PDT) efficacy using a flash wave (FW) and a continuous wave (CW) light, of which the fluence rate was 70 W/cm², for murine thymic lymphoma cells (EL-4) cultivated in vitro. The irradiation frequency and the pulse width of the FW light were in the range of 1–32 Hz and less than one millisecond, respectively. 5-Aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) was used as a photosensitizer. When EL-4 with ALA administration was irradiated by the light for 4 h (irradiation fluence: 1.0J/cm²), the survival rate of EL-4 by the FW light was lower than that by the CW light, except for the FW light with irradiation frequency of 32 Hz, and decreased gradually with decreasing irradiation frequency. Moreover, the FW light, especially at lower irradiation frequency, was superior to the CW light for the generation of singlet oxygen in an aqueous PpIX solution. Therefore, thehigher PDT efficacy for EL-4 of the FW light would be caused by the greater generation of singlet oxygen in the cells.     

荧光光谱用于光动力疗法中光敏剂光漂白特性研究

应用荧光光谱技术研究溶液中血卟啉单甲醚(HMME)的光漂白与光产物生成。以532 nm倍频Nd∶YAG激光器照射样品,功率密度为100 mW·cm-2,以光学多通道分析仪(OMA)采集荧光光谱。照光过程与荧光光谱采集同步进行。通过构建基本光谱与最小二乘拟合,由单条实测光谱中分解求得HMME荧光(613 nm)、光产物荧光(639 nm)及自体荧光的强度。HMME初始浓度不超过10 μg·mL-1时符合荧光-浓度线性函数关系。对照光过程的荧光光谱监测同时观察到HMME漂白、光产物生成与漂白,以及样品光学特性变化引起的自体荧光强度起伏。光产物漂白后的二次产物引起样品光学特性显著改变。所建立的荧光光谱探测系统与光谱分析方法可满足光敏剂漂白特性体外研究的需要,并为光动力治疗的剂量学在体监测提供有效研究方法。     

Pentacene Nanorods as Effective Photosensitizer for Photodynamic Therapy of Tumor via Singlet Fission

Singlet fission (SF), whereby a singlet exciton is converted into a pair of triplet excitons, can improve the efficiency of solar cells. Pentacene has been extensively studied as the most promising SF compound, owing to its 200% yield of triplet states. However, the easy degradation of pentacene in the presence of light and air owing to photooxidation cannot be explained by the classical ¹O₂ generation mechanism. To address this issue, in the present study, pentacene nanorods (Pc NRs) are prepared as a novel photosensitizer (PS); self-carried Pc NRs exhibited higher ¹O₂ generation capacity. Thus, a novel ¹O₂ generation mechanism is proposed based on the SF effect. The initial photon absorption occurs to access single-exciton states, S1–S3. Excited-state Pc pairs accelerate the SF effect in pentacene NRs, leading to a non-adiabatic transition to the dark D state. Dark D state is a singlet state by two triplets coupled overall, and it can transfer its energy to ³O₂ for generating ¹O₂. Using Pc NRs as PSs, photodynamic therapy (PDT) inhibits tumor growth in 4T1 tumor-bearing mice upon 405-nm-wavelength and 650-nm-wavelength laser irradiations. This study paves the way to discover novel PSs that are not considered with classical ¹O₂ generation mechanisms.     

Tumor Microenvironment Adaptable Nanoplatform for O2 Self-Sufficient Chemo/Photodynamic Combination Therapy

Malignant proliferation of tumor cells induces abnormal tissue microenvironments, leading to therapeutic resistance and poor therapeutic outcome. In this paper, manganese dioxide (MnO₂) nanoshells are coated on a porphyrinic metal–organic framework of porous coordination network (PCN)-224 for doxorubicin (DOX) loading and hyaluronic acid (HA) modification to obtain an intelligent nanoplatform of PCN@MnO₂@DOX@HA (PMDH). Benefiting from the HA functionalization, PMDH prefers to accumulate in tumor sites and enhance the cellular uptake by CD44-overexpressed tumor cells. Subsequently, the internalized PMDH could catalyze the abundant H₂O₂ in cells into O₂ to relieve tumor hypoxia. Further, the MnO₂ nanoshells of PMDH could be degraded into Mn²⁺ for magnetic resonance imaging with glutathione reduction and the release of DOX. By integrating the O₂ self-sufficiency with glutathione reduction abilities, PMDH possesses highly potent chemo/photodynamic combination therapeutic effects against hypoxic tumors. Significantly, PMDH exhibits a good biocompatibility with a low cardiotoxicity and negligible systemic side effects, which provides a new insight in developing tumor microenvironment adaptable nanoplatforms for synergistic tumor theranostics.     

Cu2SnTe3 Nanoparticles for Chemodynamic/Photodynamic /Photothermal Combination Tumor Therapy

Cancer is a serious threat to human life. However, the effect of single treatment method is limited at present. Here, a Cu₂SnTe₃ (CST) nano-reagent which can provide a strong synergetic effect in tumor therapy is successfully constructed. CST nanoparticles can not only convert endogenous H₂O₂ into ∙OH through surface-catalyzed reactions, but also generate ¹O₂ based on light irradiation-induced electron pair separation, leading to excessive oxidative stress accumulation in tumor cells. Interestingly, CST nanoparticles are also found to possess catalase-like activity, which enhances the level of O₂ within hypoxic tumors, further improving the production efficiency of ¹O₂ by photodynamic therapy (PDT). In addition, the CST nanoparticles exhibit good photothermal conversion, which facilitates to promote more ^∙OH production by chemodynamic therapy (CDT). The results of in vitro and in vivo anti-tumor experiments both demonstrate that CST nanoparticles can effectively inhibit the growth of tumor with minimal side effects. To sum up, CST nanoparticles have great potential in tumor treatment for efficient synergetic CDT/PDT/photothermal therapy.     

Synthesis,Photophysical Properties and Application of New Porphyrin Derivatives for Use in Photodynamic Therapy and Cell Imaging

New derivatives of tetrakis(4-carboxyphenyl) porphyrin were designed, synthesized and characterized by IR, proton NMR and mass spectroscopy. The ground and excited state nature of new derivatives were examined using UV-Vis. absorption and fluorescence spectroscopy, fluorescence quantum yield and fluorescence lifetime studies. The singlet oxygen quantum yield of each synthesized derivative of porphyrin was estimated for their further efficacy as potential photosensitizer in biological studies. The significant photophysical data of all synthesized derivatives was supplementary accessed to examine the cell imaging and cytotoxicity against two cancer cell lines viz. MBA-MD-231 and A375. The fluorescence lifetime, fluorescence quantum yield and efficiency of singlet oxygen generation suggests alkyl amine and alkyl hydrazide linked new porphyrin photosensitizers can be useful for PDT agent in cancer treatment.     

Improved Binary Grasshopper Optimization Algorithm for Feature Selection Problem

The migration and predation of grasshoppers inspire the grasshopper optimization algorithm (GOA). It can be applied to practical problems. The binary grasshopper optimization algorithm (BGOA) is used for binary problems. To improve the algorithm’s exploration capability and the solution’s quality, this paper modifies the step size in BGOA. The step size is expanded and three new transfer functions are proposed based on the improvement. To demonstrate the availability of the algorithm, a comparative experiment with BGOA, particle swarm optimization (PSO), and binary gray wolf optimizer (BGWO) is conducted. The improved algorithm is tested on 23 benchmark test functions. Wilcoxon rank-sum and Friedman tests are used to verify the algorithm’s validity. The results indicate that the optimized algorithm is significantly more excellent than others in most functions. In the aspect of the application, this paper selects 23 datasets of UCI for feature selection implementation. The improved algorithm yields higher accuracy and fewer features.