scholarly journals An artificial metalloenzyme for catalytic cancer-specific DNA cleavage and operando imaging

2020 ◽  
Vol 6 (29) ◽  
pp. eabb1421
Author(s):  
Liang Gao ◽  
Ya Zhang ◽  
Lina Zhao ◽  
Wenchao Niu ◽  
Yuhua Tang ◽  
...  
Keyword(s):  
Dna Cleavage ◽  
Energy Levels ◽  
High Sensitivity ◽  
Catalytic Performance ◽  
Copper Cluster ◽  
Anticancer Efficacy ◽  
Therapy Effect ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide ◽  
Artificial Metalloenzyme

Metalloenzymes are promising anticancer candidates to overcome chemoresistance by involving unique mechanisms. To date, it is still a great challenge to obtain synthetic metalloenzymes with persistent catalytic performance for cancer-specific DNA cleavage and operando imaging. Here, an artificial metalloenzyme, copper cluster firmly anchored in bovine serum albumin conjugated with tumor-targeting peptide, is exquisitely constructed. It is capable of persistently transforming hydrogen peroxide in tumor microenvironment to hydroxyl radical and oxygen in a catalytic manner. The stable catalysis recycling stems from the electron transfer between copper cluster and substrate with well-matched energy levels. Notably, their high biocompatibility, tumor-specific recognition, and persistent catalytic performance ensure the substantial anticancer efficacy by triggering DNA damage. Meanwhile, by coupling with enzyme-like reactions, the operando therapy effect is expediently traced by chemiluminescence signal with high sensitivity and sustainability. It provides new insights into synthesizing biocompatible metalloenzymes on demand to visually monitor and efficiently combat specific cancers.

A chimera of green fluorescent protein with gelatinase binding and tumor targeting peptide

2010 ◽  
Vol 72 (2) ◽  
pp. 234-237 ◽  
Author(s):  
Justus Reunanen ◽  
Tanja-Maria Ranta ◽  
Oula Peñate-Medina ◽  
Juho Suojanen ◽  
Timo Sorsa ◽  
...  
Keyword(s):  
Green Fluorescent Protein ◽  
Tumor Targeting ◽  
Fluorescent Protein ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide ◽  
Green Fluorescent

scholarly journals Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jeffry Cutrera ◽  
Denada Dibra ◽  
Arun Satelli ◽  
Xuexing Xia ◽  
Shulin Li
Keyword(s):  
Treatment Options ◽  
Tumor Model ◽  
Cytokine Gene ◽  
Tumor Models ◽  
Gene Therapies ◽  
Cytokine Gene Therapy ◽  
Tumor Environment ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide ◽  
The Impact

The safest and most effective cytokine therapies require the favorable accumulation of the cytokine in the tumor environment. While direct treatment into the neoplasm is ideal, systemic tumor-targeted therapies will be more feasible. Electroporation-mediated transfection of cytokine plasmid DNA including a tumor-targeting peptide-encoding sequence is one method for obtaining a tumor-targeted cytokine produced by the tumor-bearing patient’s tissues. Here, the impact on efficacy of the location of targeting peptide, choice of targeting peptide, tumor histotype, and cytokine utilization are studied in multiple syngeneic murine tumor models. Within the same tumor model, the location of the targeting peptide could either improve or reduce the antitumor effect of interleukin (IL)12 gene treatments, yet in other tumor models the tumor-targeted IL12 plasmid DNAs were equally effective regardless of the peptide location. Similarly, the same targeting peptide that enhances IL12 therapies in one model fails to improve the effect of either IL15 or PF4 for inhibiting tumor growth in the same model. These interesting and sometimes contrasting results highlight both the efficacy and personalization of tumor-targeted cytokine gene therapies while exposing important aspects of these same therapies which must be considered before progressing into approved treatment options.

scholarly journals Endogenous microRNA Triggered Enzyme-free DNA Logic Self-assembly for Amplified Bioimaging and Enhanced Gene Therapy via in Situ Generation of siRNAs

2021 ◽  
Author(s):  
Qinghua Jiang ◽  
Shuzhen Yue ◽  
Kaixin Yu ◽  
Tian Tian ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Self Assembly ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Dna Amplification ◽  
High Sensitivity ◽  
Free Dna ◽  
Therapy Effect ◽  
In Situ Generation

Abstract BackgroundSmall interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma.MethodsThis strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded “AND” gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma. ResultsThe proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs.ConclusionThe endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation.

scholarly journals A Yeast-Based Screening System for Differential Identification of Poison Inhibitors and Catalytic Inhibitors of Human Topoisomerase I

2021 ◽  
Author(s):  
Ahmed Seddek ◽  
Christian Madeira ◽  
Thirunavukkarasu Annamalai ◽  
Christopher Mederos ◽  
Purushottam B. Tiwari ◽  
...  
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase I ◽  
Screening System ◽  
Lethal Mutant ◽  
Anticancer Efficacy ◽  
Topological Constraints ◽  
Molecular Pattern ◽  
Anticancer Treatment ◽  
Differential Identification ◽  
Covalent Complex

Inhibition of human topoisomerase I (TOP1) by camptothecin and topotecan has been shown to reduce excessive transcription of PAMP (Pathogen-Associated Molecular Pattern) -induced genes in prior studies, preventing death from sepsis in animal models of bacterial and SARS-CoV-2 infections. The TOP1 catalytic activity likely resolves the topological constraints on DNA that encodes these genes to facilitate the transcription induction that leads to excess inflammation. The increased accumulation of TOP1 covalent complex (TOP1cc) following DNA cleavage is the basis for the anticancer efficacy of the TOP1 poison inhibitors developed for anticancer treatment. The potential cytotoxicity and mutagenicity of TOP1 targeting cancer drugs pose serious concerns for employing them as therapies in sepsis prevention. The aim of this study is to develop a novel yeast-based screening system that employs yeast strains expressing wild-type or a dominant lethal mutant recombinant human TOP1. This yeast-based screening system can identify human TOP1 poison inhibitors for anticancer efficacy as well as catalytic inhibitors that can inhibit TOP1 DNA binding or cleavage activity in steps prior to the formation of the TOP1cc. In addition to distinguishing between such TOP1 catalytic inhibitors and TOP1 poison inhibitors, results from this yeast-based screening system will also allow elimination of compounds that are likely to be cytotoxic based on their effect on yeast cell growth that is independent of recombinant human TOP1 overexpression.

scholarly journals New transitions and energy levels of water vapor by high sensitivity CRDS near 1.73 and 1.54 µm

2019 ◽  
Vol 236 ◽  
pp. 106574 ◽  
Author(s):  
S.N. Mikhailenko ◽  
E.V. Karlovets ◽  
S. Vasilchenko ◽  
D. Mondelain ◽  
S. Kassi ◽  
...  
Keyword(s):  
Water Vapor ◽  
Energy Levels ◽  
High Sensitivity

scholarly journals Application of tumor-targeting peptide-decorated polypeptide nanoparticles with doxorubicin to treat osteosarcoma

Drug Delivery ◽  
2020 ◽  
Vol 27 (1) ◽  
pp. 1704-1717
Author(s):  
Renna Qiu ◽  
Denghua Sun ◽  
Yuzhuo Bai ◽  
Jiannan Li ◽  
Lizhe Wang
Keyword(s):  
Tumor Targeting ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide

Tumor-Targeting Peptide for Redox-Responsive Pt Prodrug and Gene Codelivery and Synergistic Cancer Chemotherapy

2019 ◽  
Vol 2 (4) ◽  
pp. 1420-1426 ◽  
Author(s):  
Yaxuan Bai ◽  
Zeyu Li ◽  
Liping Liu ◽  
Tiedong Sun ◽  
Xiaocheng Fan ◽  
...  
Keyword(s):  
Cancer Chemotherapy ◽  
Tumor Targeting ◽  
Redox Responsive ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide

Abstract 5518: Bladder tumor-targeting peptide-mediated anti-tumor activity of a pro-apoptotic peptide

2010 ◽  
Author(s):  
Hyun-Kyung Jung ◽  
Mi-Kyung Kwak ◽  
Eun-Ju Lee ◽  
Ji Woong Son ◽  
Rang-Woon Park ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Bladder Tumor ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide ◽  
Anti Tumor Activity

TUMOR-TARGETING PEPTIDE-PNA-PEPTIDE CHIMERAS FOR IMAGING OVEREXPRESSED ONCOGENE mRNAS

2005 ◽  
Vol 24 (5-7) ◽  
pp. 1085-1091 ◽  
Author(s):  
X. Tian ◽  
M. R. Aruva ◽  
H. R. Wolfe ◽  
W. Qin ◽  
E. R. Sauter ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide
Sign in / Sign up

Export Citation Format

Share Document