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 application. 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 reaction 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.

ATP-triggered anticancer drug delivery

“…We anticipate that this strategy will provide new opportunities for utilizing ATP as a metabolic trigger, which can lead to the development of increasingly specific DDS. Here Dox was intercalated in the GC-rich pairs of the DNA motif; however, other drugs [51][52][53] could also be loaded into the DNA chain through their specific affinity and be released by ATP's invasion. Alternatively, drugs can be encapsulated into nanocarriers 'caged' by ATP aptamer for reversibly controlling drug release on ATP's trigger.…”

Therapeutic Applications of Spherical Nucleic Acids

“…Additionally, in nonnucleolin-expressing HBE135 cells, TMPyP4/AS1411/MNP-SNAs induced phototoxicity was significantly less than TMPyP4 only (IC 50 of TMPyP4/AS1411/ MNP-SNAs ≫3 μM vs. IC 50 of TMPyP4 only *1.5 μM). These results indicated [108]. Copyright 2013 that TMPyP4/AS1411/MNP-SNAs enabled cell-specific drug entry and acted as cytotoxic agents to nucleolin-expressing cancer cells, while protecting non-nucleolin-expressing control cells relative to TMPyP4 alone.…”

“…As such, the Tan lab sought to further expand the multimodal potential of SNAs by generating self-assembled, SNA-based constructs that combine fluorescent imaging, specific target cell recognition, and high drug loading capacity [108]. To achieve this, 30 nm streptavidin magnetic nanoparticles (MNPs) were conjugated with a biotin-DNA initiator strand that triggered a cascade of DNA-assisted hybridization reactions of monomer DNA sequences, resulting in the formation of a long DNA polymer (diameter after assembly *124 nm) as the nanoparticle shell (Fig.…”

Labeling-free fluorescent detection of DNA hybridization through FRET from pyrene excimer to DNA intercalator SYBR green I

“…During the past decades, the sequence-specific DNA detection has received great attention because of its application in many areas, such as clinical diagnosis, gene expression analysis, biomedical studies (Bi et al, 2010;Rosi et al, 2006;Sefah et al, 2009;Zheng et al, 2013b;Zhu et al, 2010). Various techniques for DNA detection have been developed, such as electrochemical (Ahangar and Mehrgardi, 2012;Ganguly et al, 2009;Qiu et al, 2011;Cheng et al, 2014) and fluorescent (Kang et al, 2009(Kang et al, , 2010Lee et al, 2014;Xiang et al, 2012;Zhang and Zhou, 2012) methods.…”