Precision spherical nucleic acids for delivery of anticancer drugs

Bousmail, Danny; Amrein, Lilian; Fakhoury, Johans; Fakih, Hassan H.; Hsu, John Chu Chia; Panasci, Lawrence C.; Sleiman, Hanadi F.

doi:10.1039/c7sc01619k

Cited by 94 publications

(93 citation statements)

References 82 publications

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“…Nanoparticles of 100-200 nm were able to encapsulate hydrophilic drugs to inhibit tumour growth. Imaging of DNA nanoparticles encapsulating buparlisib (BKM120; a PI3K inhibitor) in high efficiency for treatment of chronic lymphocytic leukaemia confirmed the spherical, near-monodispersed population of this material [71].…”

Section: Imaging and Particle Sizingmentioning

confidence: 92%

Characterization of drug delivery vehicles using atomic force microscopy: current status

Smith

Olusanya

Lamprou

2018

Expert Opinion on Drug Delivery

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Introduction: The field of nanomedicine, utilising nano-sized vehicles (nanoparticles and nanofibres) for targeted local drug delivery, has a promising future. This is dependent on the ability to analyse the chemical and physical properties of these drug carriers at the nanoscale and hence atomic force microscopy (AFM), a high-resolution imaging and local force-measurement technique, is ideally suited. Areas covered: Following a brief introduction to the technique, the review describes how AFM has been used in selected publications from 2015-2018 to characterise nanoparticles and nanofibers as drug delivery vehicles. These sections are ordered into areas of increasing AFM complexity: imaging/particle sizing, surface roughness/quantitative analysis of images and analysis of force curves (to extract nanoindentation and adhesion data). Expert opinion: AFM imaging/sizing is used extensively for the characterisation of nanoparticle and nanofibre drug delivery vehicles, with surface roughness and nanomechanical/adhesion data acquisition being less common. The field is progressing into combining AFM with other techniques, notably SEM, ToF-SIMS, Raman, Confocal and UV. Current limitations include a 50 nm resolution limit of nanoparticles imaged within live cells and AFM tip-induced activation of cytoskeleton proteins. Following drug release real-time with AFM-spectroscopic techniques and studying drug interactions on cell receptors appear to be on the horizon.

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Section: Imaging and Particle Sizingmentioning

confidence: 92%

Characterization of drug delivery vehicles using atomic force microscopy: current status

Smith

Olusanya

Lamprou

2018

Expert Opinion on Drug Delivery

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“…Nevertheless, the in vivo stability of these drug‐loaded DNA nanostructures remains a concern for this intercalation strategy. Alternatively, other studies have focused on conjugating drugs on DNA strands by chemical modification, resulting in the synthesis of DNA–drug conjugates (DDCs) for drug delivery . However, DNA–drug conjugation methods mainly rely on amino‐ and thiol‐modified DNAs, which often lead to low drug loading capability, relatively high cost, and the use of exogenously nondegradable materials as linkers.…”

Section: Methodsmentioning

confidence: 99%

Stressing the Role of DNA as a Drug Carrier: Synthesis of DNA–Drug Conjugates through Grafting Chemotherapeutics onto Phosphorothioate Oligonucleotides

et al. 2019

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To stress the role of deoxyribonucleic acid (DNA) as a drug carrier, an efficient conjugation strategy in which chemotherapeutics can be grafted onto a phosphorothiolated DNA backbone through the reaction between the phosphorothioate group (PS) and a benzyl bromide group is proposed. As a proof of concept, benzyl‐bromide‐modified paclitaxel (PTX) is employed to graft onto the DNA backbone at the PS modification sites. Due to the easy preparation of phosphorothiolated DNA at any desired position during its solid‐phase synthesis, diblock DNA strands containing both normal phosphodiester segment (PODNA) and phosphorothiolate segment (PSDNA) are directly grafted with a multitude of PTXs without using complicated and exogenous linkers. Then, the resulting amphiphilic PODNA‐blocked‐(PSDNA‐grafted PTX) conjugates (PODNA‐b‐(PSDNA‐g‐PTX)) assemble into PTX‐loaded spherical nucleic acid (SNA)‐like micellar nanoparticles (PTX‐SNAs) with a high drug loading ratio up to ≈53%. Importantly, the PODNA segment maintains its molecular recognition property and biological functions, which allows the as‐prepared PTX‐SNAs to be further functionalized with tumor‐targeting aptamers, fluorescent probe strands, or antisense sequences. These multifunctional PTX‐SNAs demonstrate active tumor‐targeting delivery, efficient inhibition of tumor growth, and the reversal of drug resistance both in vitro and in vivo for comprehensive antitumor therapy.

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“…10 The solid phase phosphoramidite method 11 used routinely to create DNA strands has recently emerged as a leading strategy for creation of truly macromolecular and sequence-defined nonnucleosidic polymers. To date, this system has been employed to modify the self-assembly and biological activity of DNA itself, [12][13][14][15][16] and as a data storage medium. [17][18][19] Shorter oligomers of chromophores produced this way display both unusual self-assembly and photonic properties.…”

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confidence: 99%

Sequence isomerism in uniform polyphosphoesters programmes self-assembly and folding

2020

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Precision spherical nucleic acids for delivery of anticancer drugs

Abstract: Highly monodisperse sequence-defined spherical nucleic acids (HE12–SNAs) for delivery of small-molecule anticancer drugs.

Cited by 94 publications

References 82 publications

Characterization of drug delivery vehicles using atomic force microscopy: current status

Characterization of drug delivery vehicles using atomic force microscopy: current status

Stressing the Role of DNA as a Drug Carrier: Synthesis of DNA–Drug Conjugates through Grafting Chemotherapeutics onto Phosphorothioate Oligonucleotides

Sequence isomerism in uniform polyphosphoesters programmes self-assembly and folding

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