Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma*

Jensen, Samuel A.; Day, Emily S.; Ko, Caroline H.; Hurley, Lisa; Luciano, Janina P.; Kouri, Fotini M.; Merkel, Timothy J.; Luthi, Andrea J.; Patel, Pinal C.; Cutler, Joshua I.; Daniel, Weston L.; Scott, A. W.; Rotz, Matthew W.; Meade, Thomas J.; Giljohann, David A.; Mirkin, Chad A.; Stegh, Alexander H.

doi:10.1201/9781003056713-106

Cited by 60 publications

(102 citation statements)

References 13 publications

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“…Spherical nucleic acids (SNAs) are clinically used nanoparticle conjugates consisting of densely packed, highly oriented, therapeutic oligonucleotides (immune-modulatory, antisense, and siRNA gene regulatory) surrounding a nanoparticle core (24)(25)(26)(27). SNAs, unlike their linear cousins, possess the ability to enter cells without the need for auxiliary transfection reagents.…”

Section: Significancementioning

confidence: 99%

Rational vaccinology with spherical nucleic acids

Wang

Qin

Yamankurt

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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124

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In the case of cancer immunotherapy, nanostructures are attractive because they can carry all of the necessary components of a vaccine, including both antigen and adjuvant. Herein, we explore how spherical nucleic acids (SNAs), an emerging class of nanotherapeutic materials, can be used to deliver peptide antigens and nucleic acid adjuvants to raise immune responses that kill cancer cells, reduce (or eliminate) tumor growth, and extend life in three established mouse tumor models. Three SNA structures that are compositionally nearly identical but structurally different markedly vary in their abilities to cross-prime antigen-specific CD8+ T cells and raise subsequent antitumor immune responses. Importantly, the most effective structure is the one that exhibits synchronization of maximum antigen presentation and costimulatory marker expression. In the human papillomavirus-associated TC-1 model, vaccination with this structure improved overall survival, induced the complete elimination of tumors from 30% of the mice, and conferred curative protection from tumor rechallenges, consistent with immunological memory not otherwise achievable. The antitumor effect of SNA vaccination is dependent on the method of antigen incorporation within the SNA structure, underscoring the modularity of this class of nanostructures and the potential for the deliberate design of new vaccines, thereby defining a type of rational cancer vaccinology.

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Section: Significancementioning

confidence: 99%

Rational vaccinology with spherical nucleic acids

Wang

Qin

Yamankurt

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

124

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“…They showed that the gene silencing can be temporally and spatially controlled using a pulsed NIR laser via lightinduced siRNA release. Jensen et al [27] complexed a high-density monolayer of siRNA on the surface of gold nanoparticles, a nanostructure so-called spherical nucleic acid (SNA), to knockdown the expression of oncoprotein Bcl2Like12 (Bcl2L12) of glioma cells. The in vitro studies showed SNAs accumulated in human glioma U87MG cells efficiently and neutralized Bcl2L12, a potent caspase and p53 inhibitor specifically overexpressed by the majority of human primary gliomas, without any chemical modifications and auxiliary transfection methods.…”

Section: Noble and Precious Metals -Properties Nanoscale Effects Andmentioning

confidence: 99%

Applications of Gold Nanoparticles in Cancer Imaging and Treatment

Wang¹,

Lu²

2018

Noble and Precious Metals - Properties, Nanoscale Effects and Applications

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Cancer is one of the leading causes of death worldwide. In the last two decades, the development of nanotechnology has facilitated our ability to design new nanoparticles for the diagnosis and treatment of cancer. In this chapter, we reviewed the applications of gold nanoparticles as contrast agents for cancer imaging, including optical imaging, photoacoustic imaging, and X-ray-based imaging. We also reviewed their applications as delivery carriers for small molecule drugs, therapeutic genes, vaccines, and adjuvants and as therapeutic agents by themselves in cancer treatment, including photothermal therapy, photodynamic therapy, and radiation therapy.

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“…Gold NPs can be in the form of nanorods, branched, nanostars, nanoclusters, nanocubes, nanospheres, nanoshells, and nanoroses, and the surfaces of these NPs can be modified to be useful for dark field imaging, photothermal therapy fluorescence imaging, drug loading, gene delivery, antigen binding, and linking to other entities. 36,37 Of the various forms of gold NP, a couple have shown enough promise to be used in clinical trials 38,39 . Of all inorganic NPs, iron oxide nanoplatforms have shown the most clinical translatability because they can be used to effectively deliver iron to treat anemia.…”

Section: Inorganic Nanoparticlementioning

confidence: 99%

Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles

Saha

Zhen

Erogbogbo

et al. 2019

Semin Thromb Hemost

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Nanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration. In this review, we present the principles underlying the structural and functional design of various classes of nanoparticles that are currently approved by the US Food and Drug Administration, categorize these particles based on their interactions with cardiovascular tissues and ensuing adverse events, and also describe various in vitro assays that may be used evaluate their hemocompatibility.

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Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma*

Cited by 60 publications

References 13 publications

Rational vaccinology with spherical nucleic acids

Rational vaccinology with spherical nucleic acids

Applications of Gold Nanoparticles in Cancer Imaging and Treatment

Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles

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