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模糊寡核苷酸的角色:作为药物递送载体的球形核酸。

Blurring the Role of Oligonucleotides: Spherical Nucleic Acids as a Drug Delivery Vehicle.

机构信息

Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.

出版信息

J Am Chem Soc. 2016 Aug 31;138(34):10834-7. doi: 10.1021/jacs.6b07554. Epub 2016 Aug 18.


DOI:10.1021/jacs.6b07554
PMID:27522867
Abstract

Nucleic acids are generally regarded as the payload in gene therapy, often requiring a carrier for intracellular delivery. With the recent discovery that spherical nucleic acids enter cells rapidly, we demonstrate that nucleic acids also have the potential to act as a delivery vehicle. Herein, we report an amphiphilic DNA-paclitaxel conjugate, which forms stable micellar nanoparticles in solution. The nucleic acid component acts as both a therapeutic payload for intracellular gene regulation and the delivery vehicle for the drug component. A bioreductively activated, self-immolative disulfide linker is used to tether the drug, allowing free drug to be released upon cell uptake. We found that the DNA-paclitaxel nanostructures enter cells ∼100 times faster than free DNA, exhibit increased stability against nuclease, and show nearly identical cytotoxicity as free drug. These nanostructures allow one to access a gene target and a drug target using only the payloads themselves, bypassing the need for a cocarrier system.

摘要

核酸通常被视为基因治疗中的有效载荷,通常需要载体进行细胞内递药。最近的研究发现,球形核酸能够快速进入细胞,这表明核酸也有可能作为递药载体。在此,我们报告了一种两亲性 DNA-紫杉醇偶联物,它在溶液中形成稳定的胶束纳米颗粒。核酸部分既作为细胞内基因调控的治疗有效载荷,又作为药物部分的递药载体。我们使用生物还原激活的自毁性二硫键连接物将药物连接起来,使得药物在细胞摄取后能够自由释放。我们发现,DNA-紫杉醇纳米结构进入细胞的速度比游离 DNA 快约 100 倍,对核酸酶的稳定性增加,并且与游离药物的细胞毒性几乎相同。这些纳米结构仅使用有效载荷本身即可同时作用于一个基因靶点和一个药物靶点,从而无需共载体系统。

相似文献

[1]
Blurring the Role of Oligonucleotides: Spherical Nucleic Acids as a Drug Delivery Vehicle.

J Am Chem Soc. 2016-8-18

[2]
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Macromol Biosci. 2011-6-29

[3]
Photolabile Self-Immolative DNA-Drug Nanostructures.

Methods Mol Biol. 2017

[4]
Construction of polymer-paclitaxel conjugate linked via a disulfide bond.

Mater Sci Eng C Mater Biol Appl. 2016-1-1

[5]
Conjugated oligomer-based fluorescent nanoparticles as functional nanocarriers for nucleic acids delivery.

ACS Appl Mater Interfaces. 2013-6-10

[6]
Drug-Loaded Polymeric Spherical Nucleic Acids: Enhancing Colloidal Stability and Cellular Uptake of Polymeric Nanoparticles through DNA Surface-Functionalization.

Biomacromolecules. 2017-2-13

[7]
Fabrication and reduction-sensitive behavior of polyion complex nano-micelles based on PEG-conjugated polymer containing disulfide bonds as a potential carrier of anti-tumor paclitaxel.

Colloids Surf B Biointerfaces. 2013-4-28

[8]
Light-triggered, self-immolative nucleic Acid-drug nanostructures.

J Am Chem Soc. 2015-5-7

[9]
Drug delivery systems based on nucleic acid nanostructures.

J Control Release. 2013-6-3

[10]
Micelle-like nanoparticles as carriers for DNA and siRNA.

Mol Pharm. 2015-2-2

引用本文的文献

[1]
Poly(lactide)-Based Materials Modified with Biomolecules: A Review.

Materials (Basel). 2024-10-24

[2]
Dynamic Light Scattering of DNA-Ligand Complexes.

Methods Mol Biol. 2024

[3]
Polymeric Nanoparticles for Drug Delivery.

Chem Rev. 2024-5-8

[4]
Spherical nucleic acids-based nanoplatforms for tumor precision medicine and immunotherapy.

Mater Today Bio. 2023-7-26

[5]
A dynamic DNA tetrahedron framework for active targeting.

Nat Protoc. 2023-4

[6]
Design of Cyclic Peptide-Based Nanospheres and the Delivery of siRNA.

Int J Mol Sci. 2022-10-11

[7]
Nucleic acid-based supramolecular structures: vesicular spherical nucleic acids from a non-phospholipid nucleolipid.

Nanoscale Adv. 2022-8-9

[8]
Maximizing TLR9 Activation in Cancer Immunotherapy with Dual-Adjuvanted Spherical Nucleic Acids.

Nano Lett. 2022-5-25

[9]
Effective delivery of paclitaxel by nanocargo of mesoporous polycaprolactone against triple negative breast cancer cells by minimalizing drug dose.

RSC Adv. 2020-6-24

[10]
Copackaging photosensitizer and PD-L1 siRNA in a nucleic acid nanogel for synergistic cancer photoimmunotherapy.

Sci Adv. 2022-4-22

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