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A spherical nucleic acid platform based on self-assembled DNA biopolymer for high-performance cancer therapy.

ABSTRACT: Based on their enhanced cellular uptake, stability, biocompatibility, and versatile surface functionalization, spherical nucleic acids (SNAs) have become a potentially useful platform in biological applications. It still remains important to expand the SNAs' "toolbox", especially given the current interest in multimodal or theranostic nanomaterials, that is, composites capable of multiple simultaneous applications such as imaging, sensing, and drug delivery. In this paper, we have engineered a nanoparticle-conjugated initiator that triggers a cascade of hybridization reactions resulting in the formation of a long DNA polymer as the nanoparticle shell. By employing different DNA fragments, self-assembled multifunctional SNAs can be constructed. Therefore, using one capped ligand, these SNAs can combine imaging fluorescent tags, target recognition element, and targeted delivery molecules together. Since these SNAs possess high drug loading capacity and high specificity by the incorporation of an aptamer, our approach might find potential applications in new drug development, existing drug improvement, and drug delivery for cancer therapy.

SUBMITTER: Zheng J

PROVIDER: S-EPMC3793642 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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A spherical nucleic acid platform based on self-assembled DNA biopolymer for high-performance cancer therapy.

Zheng Jing J Zhu Guizhi G Li Yinhui Y Li Chunmei C You Mingxu M Chen Tao T Song Erqun E Yang Ronghua R Tan Weihong W

ACS nano 20130723 8

Based on their enhanced cellular uptake, stability, biocompatibility, and versatile surface functionalization, spherical nucleic acids (SNAs) have become a potentially useful platform in biological applications. It still remains important to expand the SNAs' "toolbox", especially given the current interest in multimodal or theranostic nanomaterials, that is, composites capable of multiple simultaneous applications such as imaging, sensing, and drug delivery. In this paper, we have engineered a n ...[more]

PMID: 23841478

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Project description:Spherical nucleic acid (SNA) nanoparticle conjugates are a class of bionanomaterials that are extremely potent in many biomedical applications. Their unique ability to enter multiple mammalian cell types as single-entity agents arises from their novel three-dimensional architecture, which consists of a dense shell of highly oriented oligonucleotides chemically attached typically to a gold nanoparticle core. This architecture allows SNAs to engage certain cell surface receptors to facilitate entry. Here, we report studies aimed at determining the intracellular fate of SNAs and the trafficking events that occur inside C166 mouse endothelial cells after cellular entry. We show that SNAs traffic through the endocytic pathway into late endosomes and reside there for up to 24 h after incubation. Disassembly of oligonucleotides from the nanoparticle core is observed 16 h after cellular entry, most likely due to degradation by enzymes such as DNase II localized in late endosomes. Our observations point to these events being likely independent of core composition and treatment conditions, and they do not seem to be particularly dependent upon oligonucleotide sequence. Significantly and surprisingly, the SNAs do not enter the lysosomes under the conditions studied. To independently track the fate of the particle core and the fluorophore-labeled oligonucleotides that comprise its shell, we synthesized a novel class of quantum dot SNAs to determine that as the SNA structures are broken down over the 24 h time course of the experiment, the oligonucleotide fragments are recycled out of the cell while the nanoparticle core is not. This mechanistic insight points to the importance of designing and synthesizing next-generation SNAs that can bypass the degradation bottleneck imposed by their residency in late endosomes, and it also suggests that such structures might be extremely useful for endosomal signaling pathways by engaging receptors that are localized within the endosome.

Dataset Information

A spherical nucleic acid platform based on self-assembled DNA biopolymer for high-performance cancer therapy.

Publications

A spherical nucleic acid platform based on self-assembled DNA biopolymer for high-performance cancer therapy.

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