Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model

Purpose: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. Experimental design: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. Results: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. Conclusions: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.     

α-四(对磺酸钠苯氧基)酞菁锌(钴,镍)光敏剂的光动力性质研究

采用UV-Vis光谱、红外吸收光谱、CHN元素分析及激光解析飞行时间质谱对α-四(对磺酸钠苯氧基)酞菁锌(钴,镍)[α-PhSPcZn(Co,Ni)]进行表征.在光诱导条件下,采用四甲基偶氮唑蓝比色法(MTT法),考察了光敏剂的中心原子、浓度和光照时间等条件下对癌细胞的抑制作用.结果显示,光照15min、浓度为0~100mg·L-1范围内时,α-PhSPcZn的抑瘤率高于α-PhSPcCo和α-PhSPcNi.抑瘤率均随光照时间和配合物浓度的增加而升高,α-PhSPcZn的抑制率可达54%,其IC50值为75mg·L-1.     

DNA纳米技术研究进展

DNA不只是遗传物质,还能通过折叠形成特定的二维、三维结构,作为一种天然纳米材料可参与各种功能结构和纳米器件的构造。DNA纳米技术从被提出到现在的三十多年间,得到了飞速发展,被应用于众多领域,对纳米科学产生了重大影响。本文将主要从三种典型的DNA纳米结构和DNA纳米技术的应用两个方面进行综述,并对DNA纳米技术的前景进行展望。     

Enhancing Intersystem Crossing in Phenotiazinium Dyes by Intercalation into DNA

Phenothiazinium dyes are used as photosensitizers in photodynamic therapy. Their mode of action is related to the generation of triplet excited states by intersystem crossing. Therefore, rationalizing the factors that influence intersystem crossing is crucial to improve the efficacy of photodynamic therapy. Here we employ quantum mechanics/molecular mechanics calculations to investigate the effect of aqueous and nucleic acid environments on the intersystem crossing mechanism in methylene blue. We find that the mechanism by which the triplet states are generated depends strongly on the environment. While intersystem crossing in water is mediated exclusively by vibronic spin–orbit coupling, it is enhanced in DNA due to a second pathway driven by electronic spin–orbit coupling. Competing charge‐transfer processes, which are also possible in the presence of DNA, can therefore be suppressed by a suitable structural functionalization, thereby increasing the efficacy of photodynamic therapy.     

Diketopyrrolopyrrole‐Porphyrin Conjugates with High Two‐Photon Absorption and Singlet Oxygen Generation for Two‐Photon Photodynamic Therapy

Two‐photon photodynamic therapy is a promising therapeutic method which requires the development of sensitizers with efficient two‐photon absorption and singlet‐oxygen generation. Reported here are two new diketopyrrolopyrrole‐porphyrin conjugates as robust two‐photon absorbing dyes with high two‐photon absorption cross‐sections within the therapeutic window. Furthermore, for the first time the singlet‐oxygen generation efficiency of diketopyrrolopyrrole‐containing systems is investigated. A preliminary study on cell culture showed efficient two‐photon induced phototoxicity.     

Graphene Liquid Marbles as Photothermal Miniature Reactors for Reaction Kinetics Modulation

We demonstrate the fabrication of graphene liquid marbles as photothermal miniature reactors with precise temperature control for reaction kinetics modulation. Graphene liquid marbles show rapid and highly reproducible photothermal behavior while maintaining their excellent mechanical robustness. By tuning the applied laser power, swift regulation of graphene liquid marble’s surface temperature between 21–135 °C and its encapsulated water temperature between 21–74 °C are demonstrated. The temperature regulation modulates the reaction kinetics in our graphene liquid marble, achieving a 12‐fold superior reaction rate constant for methylene blue degradation than at room temperature.     

Multifunctional Nano‐Bioprobes Based on Rattle‐Structured Upconverting Luminescent Nanoparticles

Lanthanide‐doped upconversion nanoparticles (UCNPs) have shown great promise in versatile bioapplications. For the first time, organosilica‐shelled β‐NaLuF₄:Gd/Yb/Er nanoprobes with a rattle structure have been designed for dual‐modal imaging and photodynamic therapy (PDT). Benefiting from the unique rattle structure and aromatic framework, these nanoprobes are endowed with a high loading capacity and the disaggregation effect of photosensitizers. After loading of β‐carboxyphthalocyanine zinc or rose Bengal into the nanoprobes, we achieved higher energy transfer efficiency from UCNPs to photosensitizers as compared to those with conventional core–shell structure or with pure‐silica shell, which facilitates a large production of singlet oxygen and thus an enhanced PDT efficacy. We demonstrated the use of these nanoprobes in proof‐of‐concept X‐ray computed tomography (CT) and UC imaging, thus revealing the great potential of this multifunctional material as an excellent nanoplatform for cancer theranostics.     

牙齿组织光热动态特性仿真与试验研究

调制激光作用牙齿组织发生散射形成光子密度波, 而由于光热效应产生热波, 基于一维介质辐射传输漫射近似方程与一维热传导方程建立了调制激光作用牙齿组织半透明混合介质的一维热波数学模型. 利用该模型仿真分析了牙齿龋损特性参数(牙釉质龋损层光吸收系数、散射系数、热扩散系数及龋损深度)对光热辐射动态响应特性的影响与规律. 利用红外探测器(HgCdTe, 2–12 μm)记录808 nm半导体激光激发牙齿组织产生的热波信号, 由锁相放大器计算热波信号的幅值与相位. 通过频率扫描试验获得了牙齿组织的光热动态响应, 利用多参数最佳统计拟合方法得到了牙齿组织特性参数. 结果表明光热辐射测量对牙齿组织不均匀性和龋损特性均具有较高敏感性与特异性.     

Polymeric Gene Carriers Bearing Pendant β‐Cyclodextrin: The Relevance of Glycoside Permethylation on the “In Vitro” Cell Response

The incorporation of cyclodextrins (CDs) to nonviral cationic polymer vectors is very attractive due to recent studies that report a clear improvement of their cytocompatibility and transfection efficiency. However, a systematic study on the influence of the CD derivatization is still lacking. In this work, the relevance of β‐CD permethylation has been addressed by preparing and evaluating two series of copolymers of the cationic N‐ethyl pyrrolidine methacrylamide (EPA) and styrenic units bearing pendant hydroxylated and permethylated β‐CDs (HCDSt and MeCDSt, respectively). For both cell lines, CDs permethylation shows a strong influence on plasmid DNA complexation, “in vitro” cytocompatibility and transfection efficiency of the resulting copolymers over two murine cell lines. While the incorporation of the hydroxylated CD moiety increased the cytotoxicity of the copolymers in comparison with their homopolycationic counterpart, the permethylated copolymers have shown full cytocompatibility as well as superior transfection efficiency than the controls. This behavior has been related to the different chemical nature of both units and tentatively to a different distribution of units along the polymeric chains. Cellular internalization analysis with fluorescent copo­lymers supports this behavior.