Pure DNA scaffolded drug delivery systems for cancer therapy

Aliouat, Hanane; Peng, Ying; Waseem, Zoya; Wang, Shengfeng; Zhou, Wenhu

doi:10.1016/j.biomaterials.2022.121532

Cited by 15 publications

(5 citation statements)

References 276 publications

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“…Compared to protein enzymes, DNAzymes are compared favorably for in vivo applications owing to high chemical stability, reversible catalytic activity under harsh conditions (e.g., temperature, organic solvents, wide ranges of pHs), and ease of versatile modifications and labeling with low immunogenicity [26]. Moreover, such DNA-based biomaterials are highly biocompatible and programmable to assemble into DNA nanostructures with controlled size, shape and morphology based on the Watson-Crick base-pairing rules [29], which innovates a new field of DNAzyme-based catalytic therapy [30][31][32][33][34]. Specifically, the catalase-mimic DNAzyme has been reported, which is formed by incorporating hemin into G-rich DNA sequences, and the resulting G-quadruplex (G4)-hemin DNAzyme could effectively decompose H 2 O 2 to generate O 2 .…”

Section: Introductionmentioning

confidence: 99%

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

et al. 2022

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Photodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill tumor cells. However, the efficacy of PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, as well as tumor resistance. To tackle these issues, herein we developed a new kind of DNA nanozyme to realize enhanced PDT and synergistic tumor ferroptosis. The DNA nanozyme was constructed via rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units to form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, and chlorine e6 (Ce6), a photosensitizer, were facilely inserted into G4 structure with high efficiency, achieving in-situ catalytic oxygenation and photodynamic ROS production. Compared to other self-oxygen-supplying tools, such DNA nanozyme is advantageous for high biological stability and compatibility. Moreover, the nanostructure could achieve tumor cells targeting internalization and intranuclear transport of Ce6 by virtue of specific nucleolin binding of AS1411. The nanozyme could catalyze the decomposition of intracellular H 2 O 2 into oxygen for hypoxia relief as evidenced by the suppression of hypoxia-inducible factor-1α (HIF-1α), and moreover, GSH depletion and cell ferroptosis were also achieved for synergistic tumor therapy. Upon intravenous injection, the nanostructure could effectively accumulate into tumor, and impose multi-modal tumor therapy with excellent biocompatibility. Therefore, by integrating the capabilities of O 2 generation and GSH depletion, such DNA nanozyme is a promising nanoplatform for tumor PDT/ferroptosis combination therapy.

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Section: Introductionmentioning

confidence: 99%

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

et al. 2022

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“…Importantly, the therapeutic component may still work in the grafted form, so drug release upon delivery can be no longer necessary. Additionally, DNA with well-designed nanostructures is capable of effectively protecting oligonucleotide drugs, consequently improving their cellular transfection efficiency while diminishing their nonspecific distribution in tissue/organ. − Therefore, the oligonucleotide-grafted single-stranded DNA or nanostructure has shown great promise as a gene delivery platform and nanomedicine for cancer therapy.…”

Section: Oligonucleotide-grafted Dnamentioning

confidence: 99%

Drug-Grafted DNA for Cancer Therapy

2023

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With the development of solid-phase synthesis and DNA nanotechnology, DNA-based drug delivery systems have seen large advancements over the past decades. By combining various drugs (small-molecular drugs, oligonucleotides, peptides, and proteins) with DNA technology, drug-grafted DNA has demonstrated great potential as a promising platform in recent years, in which complementary properties of both components have been discovered; for instance, the synthesis of amphiphilic drug-grafted DNA has enabled the production of DNA nanomedicines for gene therapy and chemotherapy. Through the design of linkages between drug and DNA parts, stimuli-responsiveness can be instilled, which has boosted the application of drug-grafted DNA in various biomedical applications such as cancer therapy. This review discusses the progress of various drug-grafted DNA therapeutic agents, exploring the synthetic techniques and anticancer applications afforded through the combination of drug and nucleic acids.

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“…Therefore, the flexible programmability of building blocks fabricates a wide range of DNA architectures with precise and controllable shapes and sizes [ 19 – 21 ]. Thirdly, the addressability of DNA nanomaterial allows for the precise placement of functional groups, molecules, or nanoparticles at specific locations within the DNA nanostructure [ 22 , 23 ]. It enables the construction of multi-functional drug delivery systems for tumor-targeting delivery and therapy.…”

Section: Introductionmentioning

confidence: 99%

NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy

Yang

Zheng

et al. 2023

J Nanobiotechnol

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Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier’s endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.

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Pure DNA scaffolded drug delivery systems for cancer therapy

Cited by 15 publications

References 276 publications

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

Drug-Grafted DNA for Cancer Therapy

NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy

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