CRISPR/Cas9 and Chlorophyll Coordination Micelles for Cancer Treatment by Genome Editing and Photodynamic Therapy DOI
Chen Zhang, Xiaojie Wang,

Gengqi Liu

et al.

Small, Journal Year: 2023, Volume and Issue: 19(17)

Published: Jan. 24, 2023

Abstract CRISPR/Cas9‐based gene therapy and photodynamic both show promise for cancer treatment but still have their drawbacks limited by tumor microenvironment long duration. Herein, CRISPR/Cas9 genome editing strategy a synergistic anti‐tumor therapeutic modality is merged. Chlorophyll (Chl) extracted from natural green vegetables encapsulated in Pluronic F127 (F127) micelles Histidine‐tagged Cas9 can be effectively chelated onto via metal coordination simple incubation, affording Cas9‐Chl@F127 micelles. Mg 2+ acts as an enzyme cofactor to correlatively enhance gene‐editing activity. Upon laser irradiation, Chl effective photosensitizer generates reactive oxygen species (ROS) kill cells. Meanwhile, CRISPR/Cas9, mediated dual deliberately designed gRNAs of APE1 NRF2, reprogram the increasing intracellular accumulation impairing oxidative defense system responsively release presence abundant ATP or low pH In murine model, complexed with including NRF2 significantly inhibits growth. Taken together, micelles, representing first Chl‐based biomaterial delivery Cas9, great PDT editing.

Language: Английский

Chemodynamic Therapy via Fenton and Fenton‐Like Nanomaterials: Strategies and Recent Advances DOI

Chenyang Jia,

Yuxin Guo, Fu‐Gen Wu

et al.

Small, Journal Year: 2021, Volume and Issue: 18(6)

Published: Nov. 2, 2021

Abstract Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton‐like reaction to produce •OH in tumor region, was first proposed by Bu, Shi, and co‐workers 2016. Recently, with rapid development of nanomaterials, CDT has attracted tremendous attention because its unique advantages: 1) It is tumor‐selective low side effects; 2) process does not depend on external field stimulation; 3) it can modulate hypoxic immunosuppressive microenvironment; 4) cost low. In addition Fe‐involved strategies, reaction‐mediated strategies have also been proposed, which are based many other metal elements including copper, manganese, cobalt, titanium, vanadium, palladium, silver, molybdenum, ruthenium, tungsten, cerium, zinc. Moreover, combined therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, immunotherapy for achieving enhanced anticancer effects. Besides, there studies that extend application antibacterial field. This review introduces latest advancements nanomaterials‐involved from 2018 present proposes current limitations well future research directions related

Language: Английский

Citations

460
Strategies for enhancing cancer chemodynamic therapy performance DOI
Deblin Jana,

Yanli Zhao

Exploration, Journal Year: 2022, Volume and Issue: 2(2)

Published: March 7, 2022

Chemodynamic therapy (CDT) has emerged to be a frontrunner amongst reactive oxygen species-based cancer treatment modalities. CDT utilizes endogenous H

Language: Английский

Citations

199
Direct synthesis of amorphous coordination polymers and metal–organic frameworks DOI
Zhixing Lin, Joseph J. Richardson, Jiajing Zhou

et al.

Nature Reviews Chemistry, Journal Year: 2023, Volume and Issue: 7(4), P. 273 - 286

Published: March 6, 2023

Language: Английский

Citations

106
A Proton‐Activatable DNA‐Based Nanosystem Enables Co‐Delivery of CRISPR/Cas9 and DNAzyme for Combined Gene Therapy DOI
Feng Li, Nachuan Song, Yuhang Dong

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(9)

Published: Jan. 4, 2022

CRISPR/Cas9 is emerging as a platform for gene therapeutics, and the treatment efficiency expected to be enhanced by combination with other therapeutic agents. Herein, we report proton-activatable DNA-based nanosystem that enables co-delivery of Cas9/sgRNA DNAzyme combined therapy cancer. Ultra-long ssDNA chains, which contained recognition sequences sgRNA in Cas9/sgRNA, sequence HhaI enzyme cleavage site, were synthesized scaffold nanosystem. The cofactor Mn2+ was used compress DNA chains form nanoparticles acid-degradable polymer-coated enzymes assembled on surface nanoparticles. In response protons lysosome, polymer coating decomposed consequently exposed recognize cut off sites, thus triggering release regulate expressions achieve high efficacy breast

Language: Английский

Citations

96
An autocatalytic multicomponent DNAzyme nanomachine for tumor-specific photothermal therapy sensitization in pancreatic cancer DOI Creative Commons
Jiaqi Yan, Xiaodong Ma, Danna Liang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 30, 2023

Multicomponent deoxyribozymes (MNAzymes) have great potential in gene therapy, but their ability to recognize disease tissue and further achieve synergistic regulation has rarely been studied. Herein, Arginylglycylaspartic acid (RGD)-modified Distearyl acylphosphatidyl ethanolamine (DSPE)-polyethylene glycol (PEG) (DSPE-PEG-RGD) micelle is prepared with a DSPE hydrophobic core load the photothermal therapy (PTT) dye IR780 calcium efflux pump inhibitor curcumin. Then, MNAzyme distributed into hydrophilic PEG layer sealed phosphate through biomineralization. Moreover, RGD attached outer tail of for tumor targeting. The constructed nanomachine can release cofactor Ca2+ under acidic conditions self-assemble an active mode cleave heat shock protein (HSP) mRNA by consuming oncogene miRNA-21. Silencing miRNA-21 enhances expression suppressor PTEN, leading PTT sensitization. Meanwhile, curcumin maintains high intracellular suppress HSP-chaperone ATP disrupting mitochondrial homeostasis. Therefore, pancreatic cancer triple-sensitized IR780-mediated PTT. vitro vivo results show that MNAzyme-based strongly regulate HSP PTEN lead significant inhibition laser irradiation.

Language: Английский

Citations

75
Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions DOI Creative Commons
Haiyan Gao,

Zhiping Cao,

Huanhuan Liu

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(6), P. 1974 - 2014

Published: Jan. 1, 2023

Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate Fenton reaction or Fenton-like generate strong oxidative hydroxyl radicals tumor-specific treatment. It highly selective and safe, without depth limitation of tissue penetration, shows its potential as a new green therapeutic method with great clinical application. However, catalytic efficiency reagents involved in severely affected by inherent microenvironmental limitations tumors strict reaction-dependent conditions. With increasing application nanotechnology medical field, combined therapies based on different types functional nanomaterials have opened up avenues development next-generation CDT-enhanced system. This review will comprehensively exemplify representative results CDT other antitumor such chemotherapy, phototherapy, sonodynamic therapy, radiation magnetic hyperthermia immunotherapy, starvation gas gene oncosis combination thereof improving from hundreds latest literature, introduce strategies ingenious design nanomedicines regulations enhance further summarize challenges future perspective CDT-based multimodal anticancer therapy.

Language: Английский

Citations

66
Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy DOI Creative Commons

Shuangneng Yin,

Zhaojun Chen, Dugang Chen

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(5), P. 1520 - 1544

Published: Jan. 1, 2023

Immunotherapy has achieved great success recently and opened a new avenue for anti-tumor treatment. Programmed cell death 1/programmed ligand 1 (PD-1/PD-L1) are typical immune checkpoints that transmit coinhibitory signals, muting the host immunity. Monoclonal antibodies block PD-1/PD-L1 axis have benefited many patients with different tumor diseases. However, objective response rate is still unsatisfactory. In this review, we summarize three strategies targeting PD-L1 based on forms of various regulating mechanisms to enhance therapeutic effect, including blockade interaction between PD-1, downregulation expression degradation mature PD-L1. Thereinto, describe variety materials been designed target PD-L1, antibodies, nanoparticle, peptide, aptamer, RNA, small molecule. Additionally, list drugs regulation capacity used in clinical ongoing studies explore other alternatives besides anti-PD-L1 monoclonal antibodies. Moreover, discuss associated opportunities cancer combination therapy modalities such as chemotherapy, radiotherapy, photodynamic (PDT) photothermal (PTT), these conventional or emerging capable increasing cells by altering microenvironment (TME), would display synergistic effect. At last, give brief summary outlook regarding research status future prospect immunotherapy.

Language: Английский

Citations

65
Therapeutic DNAzymes: From Structure Design to Clinical Applications DOI Creative Commons
Jiaqi Yan, Meixin Ran, Xian Shen

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(30)

Published: Feb. 5, 2023

Therapeutic DNAzymes have unceasingly intrigued the scientific community owing to their prosperous gene regulation capability. The efficacy of against many types diseases has been extensively studied for over two decades. However, high expectations are still not translated clinic because low effectiveness in vivo. Over last five years, several aspects considered optimize DNAzyme-integrated therapeutics, including structural stability, mechanism exploration, cell internalization rate, cofactor activation, and off-target effects. Hence, this review first discusses early monotherapy design DNAzymes. Subsequently, latest modes action reviewed, followed by an elaboration on stabilization strategies considering catalytic core substrate-binding arms. DNAzyme-based synergistic therapy is then examined, highlighting responsive carrier construction, effects, discovered advanced functions, concerns. Beyond this, key clinical advances elucidated showcasing progress. Finally, future trends development challenges DNAzyme-powered therapeutics coming years discussed detail.

Language: Английский

Citations

63
Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy DOI Creative Commons
Jiaqi Yan, Rajendra Bhadane, Meixin Ran

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 1, 2024

The metal-nucleic acid nanocomposites, first termed frameworks (MNFs) in this work, show extraordinary potential as functional nanomaterials. However, thus far, realized MNFs face limitations including harsh synthesis conditions, instability, and non-targeting. Herein, we discover that longer oligonucleotides can enhance the efficiency stability of by increasing oligonucleotide folding entanglement probabilities during reaction. Besides, provide upgraded metal ions binding facilitating to load macromolecular protein drugs at room temperature. Furthermore, facilitate expansion nucleotide sequences, enabling disease-targeted MNFs. As a proof-of-concept, build an interferon regulatory factor-1(IRF-1) loaded Ca

Language: Английский

Citations

35
Metal–Drug Coordination Nanoparticles and Hydrogels for Enhanced Delivery DOI Creative Commons
Ka‐Ying Wong, Zhenyu Nie, Man‐Sau Wong

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(26)

Published: April 11, 2024

Drug delivery is a key component of nanomedicine, and conventional relies on the adsorption or encapsulation drug molecules to nanomaterial. Many vehicles contain metal ions, such as metal-organic frameworks, oxides, transition dichalcogenides, MXene, noble nanoparticles. These materials have high content pose potential long-term toxicity concerns leading difficulties for clinical approval. In this review, recent developments are summarized in use ligands coordination forming various nanomaterials soft materials. these cases, drug-to-metal ratio much higher than adsorption-based strategies. The divided into small-molecule drugs, nucleic acids, proteins. formed hybrid mainly include nanoparticles hydrogels, upon which targeting can be grafted improve efficacy further decrease toxicity. application addressing cancer, viral infection, bacterial infection inflammatory bowel disease, bone diseases reviewed. end, some future directions discussed from fundamental research, science, medicine.

Language: Английский

Citations

26