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排序方式: 共有1716条查询结果,搜索用时 187 毫秒
101.
Combinatorially Designed Lipid‐like Nanoparticles for Intracellular Delivery of Cytotoxic Protein for Cancer Therapy 下载免费PDF全文
Dr. Ming Wang Kyle Alberti Shuo Sun Carlos Luis Arellano Prof. Dr. Qiaobing Xu 《Angewandte Chemie (International ed. in English)》2014,53(11):2893-2898
An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein‐based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid‐like materials (termed “lipidoids”), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure–function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein–lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16‐1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model. 相似文献
102.
Conjugated‐Polyelectrolyte‐Based Polyprodrug: Targeted and Image‐Guided Photodynamic and Chemotherapy with On‐Demand Drug Release upon Irradiation with a Single Light Source 下载免费PDF全文
Dr. Youyong Yuan Dr. Jie Liu Prof. Dr. Bin Liu 《Angewandte Chemie (International ed. in English)》2014,53(28):7163-7168
Nanomaterials that combine diagnostic and therapeutic functions within a single nanoplatform are highly desirable for molecular medicine. Herein we report a novel theranostic platform based on a conjugated‐polyelectrolyte (CPE) polyprodrug that contains functionality for image, chemo‐ and photodynamic therapy (PDT), and on‐demand drug release upon irradiation with a single light source. Specifically, the PEGylated CPE serves as a photosensitizer and a carrier, and is covalently conjugated to doxorubicin through a linker that can be cleaved by reactive oxygen species (ROS). Under appropriate light irradiation, the CPE can generate ROS, not only for PDT, but also for on‐demand drug release and chemotherapy. This nanoplatform will offer on‐demand PDT and chemotherapy with drug release triggered by one light switch, which has great potential in cancer treatment. 相似文献
103.
Dr. Xueting Pan Dr. Weiwei Wang Dr. Zhijun Huang Shuang Liu Juan Guo Fengrong Zhang Hongjun Yuan Xin Li Prof. Fengyong Liu Prof. Huiyu Liu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(32):13659-13663
The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron–hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT. 相似文献
104.
Shaojun Yang Qiao Tang Long Chen Jin Chang Tian Jiang Jingyi Zhao Prof. Ming Wang Prof. Peng R. Chen 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(41):18243-18250
The abundance of bacterial effectors have inspired us to explore their potential in rewiring malignant cell signaling. Their incapability for entering cells, however, hinders such application. Herein we developed a cationic lipid-based high throughput library screening platform for effective intracellular delivery of bacterial effectors. As the misregulated MAPK signaling is a hallmark of many types of cancer, we turned to the Shigella effector OspF which irreversibly inactivates ERK, the terminal component of MAPK cascade. We created a function-based screening assay to obtain AMPA-O16B lipid nanoparticles for effective OspF intracellular delivery, which inhibited the malignant MAPK signaling and tumor growth in vitro and in vivo. Furthermore, the optimized lipid nanoparticle formulation can deliver OspF to modulate the immunosuppressive responses in macrophages. Our work is a general strategy to explore the therapeutic potentials of naturally evolved bacterial effectors. 相似文献
105.
Ruibing An Xiaoyang Cheng Shixuan Wei Yuxuan Hu Yidan Sun Zheng Huang Prof. Hong-Yuan Chen Prof. Deju Ye 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(46):20817-20825
Stimuli-responsive smart photosensitizer (PS) nanoassemblies that allow enhanced delivery and controlled release of PSs are promising for imaging-guided photodynamic therapy (PDT) of tumors. However, the lack of high-sensitivity and spatial-resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo. Herein, we report tumor targeting, redox-responsive magnetic and fluorogenic PS nanoassemblies ( NP-RGD ) synthesized via self-assembly of a cRGD- and disulfide-containing fluorogenic and paramagnetic small molecule ( 1-RGD ) for fluorescence/magnetic resonance bimodal imaging-guided tumor PDT. NP-RGD show high r1 relaxivity but quenched fluorescence and PDT activity; disulfide reduction by glutathione (GSH) promotes efficient disassembly into a small-molecule probe ( 2-RGD ) and an organic PS (PPa-SH), which could further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors. 相似文献
106.
Dr. Yongxin Li Pan Sun Luyang Zhao Prof. Xuehai Yan Prof. Dennis K. P. Ng Prof. Pui-Chi Lo 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(51):23428-23438
A facile approach to assemble catalase-like photosensitizing nanozymes with a self-oxygen-supplying ability was developed. The process involved Fe3+-driven self-assembly of fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids. By adding a zinc(II) phthalocyanine-based photosensitizer (ZnPc) and the hypoxia-inducible factor 1 (HIF-1) inhibitor acriflavine (ACF) during the Fe3+-promoted self-assembly of Fmoc-protected cysteine (Fmoc-Cys), the nanovesicles Fmoc-Cys/Fe@Pc and Fmoc-Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly. The released Fe3+ could catalyze the transformation of H2O2 enriched in cancer cells to oxygen efficiently, thereby ameliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc-Cys/Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc-Cys/Fe@Pc, demonstrating the synergistic effect of ZnPc and ACF. 相似文献
107.
Chaonan Mu Wei Wang Jie Wang Chu Gong Dongmei Zhang Prof. Dr. Xinxing Zhang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(48):21699-21703
While Type I and Type II photosensitizers are often carefully tailored to achieve their respective advantages in treating different cancers, the identifications of the Type I and II mechanisms as such, the key reaction intermediates, and the consequent oxidation products of the substrates have never been easy. Using our unique home-built field-induced droplet ionization mass spectrometry (FIDI-MS) method that selectively samples molecules at the air–water interface, here we show the facile determination of both Type I and II mechanisms of a poster-child photosensitizer, temoporfin, without the addition of any probes. The unstable doublet radical resulting from the hydrogen abstraction by the triplet temoporfin through the Type I mechanism is captured, manifesting the in situ advantage of FIDI-MS. We anticipate that the method developed in this study can be widely utilized in the future designs of novel photosensitizers and the screening of their photosensitization mechanisms. 相似文献
108.
Photodynamic therapy (PDT) has been received broad attentions as a cancer treatment, and fullerenes are potential photosensitizer owing to their unique electronic structures. However, fullerenes show insolubility in water for the special structure, which will induce aggregation to hinder the production of reactive oxygen species (ROS). Furthermore, the size of fullerenes is not conducive to reach the tumors through the enhanced permeability and retention (EPR) effect. Herein, a polyhydroxy fullerene-loaded metal-organic framework is designed and prepared to address the mentioned problems encountering with fullerenes as photosensitizers. The nanocomposite PHF@ZIF-8, which is synthesized by a simple one-pot method, displays great biocompatibility and outstanding photodynamic performance under the 448 nm laser irradiation. This work provides strong evidence for PHF@ZIF-8 as a promising photosensitizer candidate. 相似文献
109.
活性氧响应型抗肿瘤前药研究进展 总被引:1,自引:0,他引:1
活性氧(ROS)在机体信号转导和代谢中起着至关重要的作用,而ROS水平的升高与多种病变(癌症和炎症等)息息相关,基于肿瘤组织高水平ROS开发的肿瘤特异杀伤性前药策略,在增强药效和药物选择性方面提供了一种新颖的方法.本综述介绍了目前用于构建抗肿瘤前药的ROS敏感键:芳基硼酸/酯、烷基硫/硒醚、硫缩酮、过氧草酸酯、氨基丙烯酸酯、噻唑烷酮和α-酮酰胺等,并且详叙了基于这些敏感键设计的前药在抗肿瘤方向上的应用,同时探讨了现有ROS响应型前药系统的研究进展和局限性,并对未来的研究方向进行了展望. 相似文献
110.
Greta Linden Prof. Dr. Olalla Vázquez 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(44):10014-10023
Photodynamic therapy (PDT) leads to cancer remission via the production of cytotoxic species under photosensitizer (PS) irradiation. However, concomitant damage and dark toxicity can both hinder its use. With this in mind, we have implemented a versatile peptide-based platform of bioorthogonally activatable BODIPY-tetrazine PSs. Confocal microscopy and phototoxicity studies demonstrated that the incorporation of the PS, as a bifunctional module, into a peptide enabled spatial and conditional control of singlet oxygen (1O2) generation. Comparing subcellular distribution, PS confined in the cytoplasmic membrane achieved the highest toxicities (IC50=0.096±0.003 μm ) after activation and without apparent dark toxicity. Our tunable approach will inspire novel probes towards smart PDT. 相似文献