具有叶绿素-a碳架的(细菌)卟吩衍生物的合成及其共轭区域变化对光谱性能的影响

以脱镁叶绿酸-a甲酯(MP-a) (1)为起始原料, 通过四氧化锇和高碘酸钠的氧化给出3-位乙烯基和13²-位α-氢的氧化产物2和3, 再用四氧化锇继续氧化卟吩醛2则得到细菌卟吩醛4. 经脱甲酸甲酯和硝酸铊氧化, MP-a (1)转化为焦脱镁叶绿酸衍生物5, 将其进一步用四氧化锇氧化则形成细菌卟吩缩醛6. 卟吩醛2在碱性条件下转化为卟吩e₆三甲酯7, 2与烷基溴化镁的格氏反应给出脱镁叶绿酸醇9, 选择高钌酸四丙基铵(TPAP)和N-甲基吗啉N-氧化物将3-位羟基氧化成羰基, 所生成的卟吩二酮10在酸性条件下脱去甲酸甲酯生成焦脱镁叶绿酸衍生物11, 用四氧化锇对7和11实施氧化, 则分别转化为细菌卟吩衍生物8和12. 同时, 讨论了叶绿素衍生物的共轭区域变化对其光谱性能的影响. 所合成的新卟吩和细菌卟吩衍生物均经UV, IR, ¹H NMR及元素分析证明其结构.     

水溶性IR-780聚合物用于线粒体靶向的光动力治疗※

11-氯-1,1'-二正丙基-3,3,3',3'-四甲基-10,12-三亚甲基吲哚三碳花青碘盐(IR-780)被具有较强组织穿透能力的近红外光照射后, 能快速高效地产生活性氧, 导致细胞死亡, 可用于光动力治疗. 但是IR-780的水溶性差, 这极大限制了其生物医学应用. 基于此我们设计合成了可高效靶向线粒体的水溶性IR-780聚合物Poly-IR, Poly-IR在水中自组装成为纳米粒子. Poly-IR纳米粒子受近红外光激活后, 在肿瘤细胞内外均能快速高效地产生活性氧, 并且该纳米粒子能够在线粒体中富集, 受近红外光的激发后产生的活性氧能够破坏线粒体, 导致线粒体膜电位降低. 细胞毒性、活死细胞染色及凋亡实验结果也进一步证明, 该纳米粒子在近红外光照下能够有效地抑制肿瘤细胞的增殖. 本体系为靶向线粒体的光动力治疗肿瘤领域拓展了思路.     

Active Targeting of Tumors through Conformational Epitope Imprinting

Inspired by the knowledge that most antibodies recognize a conformational epitope because of the epitope’s specific three‐dimensional shape rather than its linear structure, we combined scaffold‐based peptide design and surface molecular imprinting to fabricate a novel nanocarrier harboring stable binding sites that captures a membrane protein. In this study, a disulfide‐linked α‐helix‐containing peptide, apamin, was used to mimic the extracellular, structured N‐terminal part of the protein p32 and then serve as an imprinting template for generating a sub‐40 nm‐sized polymeric nanoparticle that potently binds to the target protein, recognizes p32‐positive tumor cells, and successfully mediates targeted photodynamic therapy in vivo. This could provide a promising alternative for currently used peptide‐modified nanocarriers and may have a broad impact on the development of polymeric nanoparticle‐based therapies for a wide range of human diseases.     

近红外光激发功能化上转换纳米颗粒用于解聚Aβ聚集体

阿尔兹海默症(AD)是一种进行性神经退行性疾病, 其特征是记忆力减退、神志不清和各种认知障碍. β-淀粉样蛋白(Aβ)的自组装聚集是阿尔茨海默症患者大脑的主要特征之一, 其加剧了AD患者的神经病变和认知障碍, 因此抑制Aβ聚集是一种潜在的治疗AD的策略. 光动力疗法是抑制Aβ聚集和解聚Aβ聚集体的有效方法. 然而, 大多数光敏剂为紫外和可见光激发, 在生物组织中的渗透深度低, 并引起严重的组织损伤, 这限制了其在生物医学中的应用. 本工作构建了一种近红外光激发的双靶向上转换纳米体系应用于抑制Aβ聚集过程. 以核壳结构的上转换纳米颗粒(UCNPs)作为光转换器, 通过两亲聚合物二硬脂酰基磷脂酰乙醇胺-聚乙二醇-马来酰亚胺(DSPE-PEG-MAL)的疏水包覆作用负载光敏剂二氢卟吩e6 (Ce6), 在纳米颗粒表面通过马来酰亚胺与巯基的特异性反应修饰了可跨越血脑屏障的肽链TGN和靶向Aβ₄₂的肽链QSH. 实验结果表明在近红外光激发下UCNPs通过发光共振能量转移(LRET)将能量转移至光敏剂Ce6, 使其跃迁至激发态后与周围的氧气分子作用产生单线态氧(¹O₂), 不可逆地氧化Aβ, 从而有效解聚了Aβ聚集体, 降低了Aβ聚集体的神经毒性. 此外, 该体系不仅具有良好的生物相容性, 而且可以有效穿过血脑屏障靶向作用于Aβ₄₂, 显示出其在活体水平治疗AD的潜力.     

Unraveling the Photodynamic Activity of Cationic Benzoporphyrin-Based Photosensitizers against Bladder Cancer Cells

In this study, we report the preparation of new mono-charged benzoporphyrin complexes by reaction of the appropriate neutral benzoporphyrin with (2,2′-bipyridine)dichloroplatinum(II) and of the analogs’ derivatives synthesized through alkylation of the neutral scaffold with iodomethane. All derivatives were incorporated into polyvinylpyrrolidone (PVP) micelles. The ability of the resultant formulations to generate reactive oxygen species was evaluated, mainly the singlet oxygen formation. Then, the capability of the PVP formulations to act as photosensitizers against bladder cancer cells was assessed. Some of the studied formulations were the most active photosensitizers causing a decrease in HT-1376 cells’ viability. This creates an avenue to further studies related to bladder cancer cells.     

以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究进展

光动力疗法作为一种非侵入性治疗手段已广泛应用于肿瘤的临床治疗。然而其疗效却深受紫外-可见光组织穿透深度的限制。镧系掺杂上转换纳米颗粒可以将近红外光转换为紫外-可见光,被广泛用于与传统光敏剂结合实现更为高效的光动力治疗。近年来,以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究备受关注,本文重点介绍了该领域的最新研究进展,并对其未来发展方向作出了展望。     

含碘二氧化硅纳米颗粒对BODIPY染料光动力效果的影响

利用含碘硅烷前体制备包裹BODIPY染料分子的纳米二氧化硅颗粒.颗粒中的碘原子通过重原子效应有效提高了BODIPY染料分子的系间窜越效率,进而提高了染料分子的单重态氧量子产率及光损伤DNA的能力.这一结果表明,含碘二氧化硅纳米颗粒可以成为众多荧光染料分子在光动力疗法领域应用的一个有效药物负载和输送体系.     

菁染料在荧光探针及光动力疗法中的应用

菁染料的研究及应用已有100多年的历史,近年来,它们在生物方面的应用研究已取得一定的成果.本文就近几年菁染料及其衍生物在生物医疗方面的研究及进展情况加以综述,特别阐述了这类染料用作荧光探针在生物大分子标识以及作为光敏剂在光动力疗法(PDT)中用于恶性肿瘤的诊断与治疗这两方面的研究进展.     

Biomimetic Cascade Polymer Nanoreactors for Starvation and Photodynamic Cancer Therapy

The selective disruption of nutritional supplements and the metabolic routes of cancer cells offer a promising opportunity for more efficient cancer therapeutics. Herein, a biomimetic cascade polymer nanoreactor (GOx/CAT-NC) was fabricated by encapsulating glucose oxidase (GOx) and catalase (CAT) in a porphyrin polymer nanocapsule for combined starvation and photodynamic anticancer therapy. Internalized by cancer cells, the GOx/CAT-NCs facilitate microenvironmental oxidation by catalyzing endogenous H₂O₂ to form O₂, thereby accelerating intracellular glucose catabolism and enhancing cytotoxic singlet oxygen (¹O₂) production with infrared irradiation. The GOx/CAT-NCs have demonstrated synergistic advantages in long-term starvation therapy and powerful photodynamic therapy (PDT) in cancer treatment, which inhibits tumor cells at more than twice the rate of starvation therapy alone. The biomimetic polymer nanoreactor will further contribute to the advancement of complementary modes of spatiotemporal control of cancer therapy.     

Application of TD-DFT Theory to Studying Porphyrinoid-Based Photosensitizers for Photodynamic Therapy: A Review

An important focus for innovation in photodynamic therapy (PDT) is theoretical investigations. They employ mostly methods based on Time-Dependent Density Functional Theory (TD-DFT) to study the photochemical properties of photosensitizers. In the current article we review the existing state-of-the-art TD-DFT methods (and beyond) which are employed to study the properties of porphyrinoid-based systems. The review is organized in such a way that each paragraph is devoted to a separate aspect of the PDT mechanism, e.g., correct prediction of the absorption spectra, determination of the singlet–triplet intersystem crossing, and interaction with molecular oxygen. Aspects of the calculation schemes are discussed, such as the choice of the most suitable functional and inclusion of a solvent. Finally, quantitative structure–activity relationship (QSAR) methods used to explore the photochemistry of porphyrinoid-based systems are discussed.