Benzoporphyrins and Acetylene-Substituted Porphyrins as Improved Photosensitizers in the Photodynamic Tumor Therapy with Porphyrin Platinum Conjugates

Summary.  A combination of a cisplatinum-like fragment and a porphyrin in the same molecule should not only result in the additivity of the dark toxicity of the platinum fragment and the phototoxicity of the porphyrin moiety, but also in the enrichment of the porphyrin platinum conjugates in tumor tissue, which cisplatinum alone does not show. To increase the penetration depth of the red light used in the photodynamic tumor therapy the conjugated system of the porphyrin components in porphyrin platinum conjugates had to be expanded. Sixteen new (NH₃)₂Pt derivatives of benzoporphyrins and acetylene-substituted porphyrins were synthesized, characterized, and tested with respect to their antitumor activity on the mammary carcinoma cell line MDA-MB-231. Received November 12, 2001. Accepted November 20, 2001     

共价有机框架的合成及其在肿瘤治疗中的应用研究进展

共价有机框架(covalentorganicframeworks,COFs)是近年来开发的一种由有机单元连接而成的高结晶性多孔聚合物,由于具有良好的孔隙率、模块性、结晶性和生物相容性等特点在肿瘤治疗中显示出了良好的应用前景.本综述总结了已报道的COFs制备方法,包括溶剂热合成法、机械化学合成法、微波合成法、离子热合成法、界面合成法、室温合成法和纳米尺度COFs的合成方法,并根据对肿瘤作用机理的差异,将用于肿瘤治疗的COFs纳米载药系统归纳为药物化疗、光热治疗、光动力学治疗和联合治疗.此外还讨论了COFs在肿瘤治疗领域所面临的主要挑战和发展趋势.     

Chemiluminescence and Bioluminescence as an Excitation Source in the Photodynamic Therapy of Cancer: A Critical Review

Photodynamic therapy (PDT) of cancer is known for its limited number of side effects, and requires light, oxygen and photosensitizer. However, PDT is limited by poor penetration of light into deeply localized tissues, and the use of external light sources is required. Thus, researchers have been studying ways to improve the effectiveness of this phototherapy and expand it for the treatment of the deepest cancers, by using chemiluminescent or bioluminescent formulations to excite the photosensitizer by intracellular generation of light. The aim of this Minireview is to give a précis of the most important general chemi‐/bioluminescence mechanisms and to analyze several studies that apply them for PDT. These studies have demonstrated the potential of utilizing chemi‐/bioluminescence as excitation source in the PDT of cancer, besides combining new approaches to overcome the limitations of this mode of treatment.     

有序介孔二氧化硅纳米粒的制备及其肿瘤诊疗应用

有序介孔二氧化硅纳米粒由于具有独特的结构特征和物理化学性质,能够与磁性材料、荧光探针、抗肿瘤药物和特异性生物靶向分子等相结合,从而实现有序介孔二氧化硅纳米粒的多功能化,现已逐步应用于肿瘤的诊断和治疗等生物医学领域。本文就有序介孔二氧化硅纳米粒在制备、表面修饰及应用等几个方面的最新研究进展进行了综述。首先,重点介绍了不同pH条件下制备有序介孔二氧化硅纳米粒的方法和模板剂脱除方法,并简单归纳了各种方法的优缺点;其次,简要介绍了其表面稳定化和功能化修饰的研究现状,以及负载影像试剂和化疗药物的有序介孔二氧化硅纳米粒在肿瘤的多模成像诊断和靶向治疗中的应用进展;最后,总结了目前研究中还存在的问题并展望了其未来发展方向。     

超声弹性成像参数联合血清MK和VEGF对分化型甲状腺癌的诊断价值及与肿瘤恶性程度关系研究

本研究选取了分化型甲状腺癌(DTC)患者106例为甲状腺癌组,同期106例甲状腺腺瘤患者为甲状腺腺瘤组,检测比较了两组患者的超声弹性成像参数(弹性比值、蓝色面积比值)、血清中期因子(midkine,MK)、血管内皮生长因子(VEGF)水平.研究结果发现,弹性比值、蓝色面积比值、血清MK和VEGF水平与DTC患者淋巴结转...     

Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of 193mPt and 195mPt Radionuclides in Auger Electron Therapy

^193mPt and ^195mPt radionuclides are therapeutically attractive Auger electron emitters with notably high Auger electron yield per decay. The present paper summarizes the first step of research on the applications of core-shell (Au@Pt) nanoparticles for electron Auger therapy of HER2+ (human epidermal growth factor receptor 2) breast cancer and hepatocellular carcinoma. Gold nanoparticles (30 nm) were synthesized covered with a platinum shell at high efficiency (>80%) and were further evaluated for in vitro studies such as binding affinity, internalization and cytotoxicity. To find the mechanism(s) responsible for platinum cytotoxicity in HepG2 cells, the platinum concentration in isolated cell nuclei and cytoplasm was determined using ICP-MS (inductively coupled plasma mass spectrometry). Lack of platinum in cell nuclei suggests that the cytotoxic effect is associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Studies carried out on the SKOV-3 cell line with the use of a synthesized targeting bioconjugate (Au@Pt-PEG-trastuzumab) revealed a high affinity of this preparation to HER2+ cells, its internalization, its placement in the perinuclear area and partial intranuclear location. The specific binding for HER2 negative cells, MDA-MB-231, was negligible and Au@Pt-PEG-trastuzumab did not enter these cells. The results obtained are promising and warrant future investigation of Auger electron therapy using ^193mPt and ^195mPt based radiopharmaceuticals.     

Broussochalcone A Is a Novel Inhibitor of the Orphan Nuclear Receptor NR4A1 and Induces Apoptosis in Pancreatic Cancer Cells

The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth. In this study, we identified broussochalcone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells. BCA downregulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway. These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.