Theranostic barcoded nanoparticles for personalized cancer medicine

Yaari, Zvi; Silva, Dana da; Zinger, Assaf; Goldman, Evgeniya; Kajal, Ashima; Tshuva, Rafi; Barak, Eran Cohen; Dahan, Nitsan; Hershkovitz, Dov; Goldfeder, Mor; Roitman, Janna; Schroeder, Avi

doi:10.1038/ncomms13325

Cited by 115 publications

(103 citation statements)

References 58 publications

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“…By incorporating deep sequencing, our approach dramatically increases the number of particles that can be simultaneously measured, as well as improves the sensitivity, specificity, and accuracy of those measurements. Our work, as well as DNA barcoded particles that were shown to target tumors, demonstrates the power of unbiased in vivo approaches (30). Notably, this platform is distinct from previous reports, which conjugate nucleic acids to the exterior of particles to fluorescently label them or use them to identify known pathogenic DNA sequences in bodily fluids (31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 80%

Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics

Dahlman

Kauffman

Xing

et al. 2017

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

193

200

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Nucleic acid therapeutics are limited by inefficient delivery to target tissues and cells and by an incomplete understanding of how nanoparticle structure affects biodistribution to off-target organs. Although thousands of nanoparticle formulations have been designed to deliver nucleic acids, most nanoparticles have been tested in cell culture contexts that do not recapitulate systemic in vivo delivery. To increase the number of nanoparticles that could be tested in vivo, we developed a method to simultaneously measure the biodistribution of many chemically distinct nanoparticles. We formulated nanoparticles to carry specific nucleic acid barcodes, administered the pool of particles, and quantified particle biodistribution by deep sequencing the barcodes. This method distinguished previously characterized lung-and liver-targeting nanoparticles and accurately reported relative quantities of nucleic acid delivered to tissues. Barcode sequences did not affect delivery, and no evidence of particle mixing was observed for tested particles. By measuring the biodistribution of 30 nanoparticles to eight tissues simultaneously, we identified chemical properties promoting delivery to some tissues relative to others. Finally, particles that distributed to the liver also silenced gene expression in hepatocytes when formulated with siRNA. This system can facilitate discovery of nanoparticles targeting specific tissues and cells and accelerate the study of relationships between chemical structure and delivery in vivo.barcode | nanotechnology | nanoparticle | drug delivery | gene therapy

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Section: Discussionmentioning

confidence: 80%

Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics

Dahlman

Kauffman

Xing

et al. 2017

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

193

200

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“…Actually, NPs can sufficiently disperse in aqueous solution and, thanks to their dimensions ranging from 1 to 200 nm, have more changes to avoid the activation of the complement cascade and their eventual clearance by immune cells and macrophages [20]. The fast nanotechnological evolution in the production of different kinds of NPs supports early disease diagnosis and staging, thus enabling also image-guided therapy and personalized therapy [192][193][194][195][196]. NPs application in theranostics allows to integrate diagnostic and therapeutic capabilities into a single nanostructure.…”

Section: Clinical Applications Of Nps Assisted Ultrasound In Cancer Tmentioning

confidence: 99%

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

Canavese

Ancona

Racca

et al. 2018

Chemical Engineering Journal

302

247

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• Ultrasound-based therapies are opening new horizons in the oncological field.• Innovative and promising solutions derive from different nanoparticles-assisted ultrasound treatments.• Sonodynamic therapy (SDT) emerged recently as a novel approach for cancer treatment.• Different and complex cell death mechanisms are involved in nanoparticles-assisted SDT.• Nanoparticles-assisted ultrasound is still at its infancy in clinics. A R T I C L E I N F O Keywords:Inertial cavitation Reactive oxygen species Sonoluminescence Sonodynamic Tumor Therapy Cytotoxicity A B S T R A C TAt present, ultrasound radiation is broadly employed in medicine for both diagnostic and therapeutic purposes at various frequencies and intensities. In this review article, we focus on therapeutically-active nanoparticles (NPs) when stimulated by ultrasound. We first introduce the different ultrasound-based therapies with special attention to the techniques involved in the oncological field, then we summarize the different NPs used, ranging from soft materials, like liposomes or micro/nano-bubbles, to metal and metal oxide NPs. We therefore focus on the sonodynamic therapy and on the possible working mechanisms under debate of NPs-assisted sonodynamic treatments. We support the idea that various, complex and synergistics physical-chemical processes take place during acoustic cavitation and NP activation. Different mechanisms are therefore responsible for the final cancer cell death and strongly depends not only on the type and structure of NPs or nanocarriers, but also on the way they interact with the ultrasonic pressure waves. We conclude with a brief overview of the clinical applications of the various ultrasound therapies and the related use of NPs-assisted ultrasound in clinics, showing that this very innovative and promising approach is however still at its infancy in the clinical cancer treatment.

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“…One multiplexed signal that has been used by groups (including ours) is DNA [33,45,46]. DNA is an excellent molecule for multiplexing.…”

Section: Nanoparticle Barcoding Enables Simultaneous Analysis Of >100mentioning

confidence: 99%

“…In one example, DNA was formulated into liposomes alongside different chemotherapies [45] (Fig. 2B).…”

Section: Nanoparticle Barcoding Enables Simultaneous Analysis Of >100mentioning

confidence: 99%

Testing thousands of nanoparticles in vivo using DNA barcodes

Lokugamage

Sago

Dahlman

2018

Current Opinion in Biomedical Engineering

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Nanoparticles improve drug efficacy by delivering drugs to sites of disease. To effectively deliver a drug in vivo, a nanoparticle must overcome physical and physiological hurdles that are not present in cell culture, yet in vitro screens are used to predict nanoparticle delivery in vivo. An ideal nanoparticle discovery pipeline would enable scientists to study thousands of nanoparticles in vivo. Here, we discuss technologies that enable high throughput in vivo screens, focusing on DNA barcoded nanoparticles.

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Theranostic barcoded nanoparticles for personalized cancer medicine

Cited by 115 publications

References 58 publications

Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics

Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

Testing thousands of nanoparticles in vivo using DNA barcodes

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