Using Gold Nanoparticles as Delivery Vehicles for Targeted Delivery of Chemotherapy Drug Fludarabine Phosphate to Treat Hematological Cancers

Song, Steven; Hao, Yuzhi; Yang, Xiaoyan; Patra, Prabir; Chen, Jie

doi:10.1166/jnn.2016.12349

Cited by 37 publications

(25 citation statements)

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“…Despite the high anti‐proliferative effect of free TS262 and TS265 in FR37‐CMT cells, it has been demonstrated that AuNPs are excellent carriers for drug delivery . To allow the direct comparison between free and nanoconjugated compounds, the effect of the NanoTS262 and NanoTS265 on FR37‐CMT cells viability was performed at IC 50 concentrations, both for the free compounds and the nanovectorized.…”

Section: Resultsmentioning

confidence: 99%

“…The high cytotoxic effect here demonstrated for the free TS262 and TS265 in the FR37‐CMT cell line, highlights their further application using novel nanodelivery systems. Owing to their size and ease of functionalization with different moieties (eg PEG for biocompatibility; BSA allowing the loading with the desired chemotherapeutics—here TS262 or TS265 as models) it has been demonstrated that AuNPs can act as promising carriers for drug delivery further increasing the therapeutic index . Despite the high number of applications of AuNPs as drug delivery agents in human cancer, as far as we are aware there is no description of their application in CMT.…”

Section: Discussionmentioning

confidence: 99%

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Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds

Raposo

Roma‐Rodrigues²,

Jesus³

et al. 2017

Vet Comparative Oncology

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds

Raposo

Roma‐Rodrigues²,

Jesus³

et al. 2017

Vet Comparative Oncology

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“…However, biological delivery methods are highly cargo and host-specific (6) whereas particle bombardment can result in tissue damage (7). Nanomaterial-mediated biomolecule delivery has facilitated genetic engineering and biosynthetic pathway mapping in animal systems (8)(9)(10)(11)(12), but has only recently been explored for plants. Specifically, two recent studies have shown that carbon nanotubes (13) and clay nanosheets (14) enable passive intracellular delivery of DNA and RNA through surface-grafting or encapsulation strategies, circumventing the use of biolistics (external force).…”

Section: Introductionmentioning

confidence: 99%

DNA Nanostructures Coordinate Gene Silencing in Mature Plants

Zhang

Demirer

Zhang

et al. 2019

Preprint

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SignificancePlant bioengineering will be necessary to sustain plant biology and agriculture, where the delivery of biomolecules such as DNA, RNA, or proteins to plant cells is at the crux of plant biotechnology. Here, we show that DNA nanostructures can passively internalize into plant cells and deliver small interfering RNA (siRNA) to mature plant tissues. Furthermore, we demonstrate that nanostructure size, shape, compactness, and stiffness, affect both nanostructure internalization into plant cells and subsequent gene silencing efficiency. Interestingly, we also find that the siRNA attachment locus affects the endogenous plant gene silencing pathway. Our work demonstrates programmable passive delivery of biomolecules to plants, and details the figures of merit for future implementation of DNA nanostructures in agriculture. AbstractPlant bioengineering may generate high yielding and stress-resistant crops amidst a changing climate and a growing global population (1-3). However, delivery of biomolecules to plants relies on Agrobacterium infection (4) or biolistic particle delivery (5), the former of which is only amenable to DNA delivery. The difficulty in delivering functional biomolecules such as RNA to plant cells is due to the plant cell wall which is absent in mammalian cells and poses the dominant physical barrier to exogenous biomolecule delivery in plants. DNA nanostructure-mediated biomolecule delivery is an effective strategy to deliver cargoes across the lipid bilayer of mammalian cells, however, nanoparticle-mediated delivery remains unexplored for passive biomolecule delivery across the cell wall in plants. Herein, we report a systematic assessment of different DNA nanostructures for their ability to internalize into cells of mature plants, deliver small interfering RNAs (siRNAs), and effectively silence a constitutivelyexpressed gene in Nicotiana benthamiana leaves. We show that nanostructure internalization into plant cells and the corresponding gene silencing efficiency depends on the DNA nanostructure size, shape, compactness, stiffness, and location of the siRNA attachment locus on the nanostructure. We further confirm that the internalization efficiency of DNA nanostructures correlates with their respective gene silencing efficiencies, but that the endogenous gene silencing pathway depends on the siRNA attachment locus. Our work establishes the feasibility of biomolecule delivery to plants with DNA nanostructures, and details both the design parameters of importance for plant cell internalization, and also assesses the impact of DNA nanostructure geometry for gene silencing mechanisms.

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“…While nanoparticle-mediated delivery of genes, RNAs, and therapeutics has been extensively explored in animals 15,16 , their potential for plant systems remains understudied 17 . Several prior studies take advantage of nanomaterials to deliver plasmid DNA [18][19][20][21] or proteins 22 to intact plant cells.…”

Section: Introductionmentioning

confidence: 99%

Nanotubes effectively deliver siRNA to intact plant cells and protect siRNA against nuclease degradation

Demirer¹,

Zhang²,

Goh³

et al. 2019

Preprint

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Post-transcriptional gene silencing (PTGS) is a powerful tool to understand and control plant metabolic pathways, which is central to plant biotechnology. PTGS is commonly accomplished through delivery of small interfering RNA (siRNA) into cells. While siRNA delivery has been optimized for mammalian systems, it remains a significant challenge for plants due to the plant cell wall. Standard plant siRNA delivery methods (Agrobacterium and viruses) involve coding siRNA into DNA vectors, and are only tractable for certain plant species. Herein, we develop a nanotube-based platform for direct delivery of siRNA, and show high silencing efficiency in intact plant cells. We demonstrate that nanotubes successfully deliver siRNA and silence endogenous genes owing to effective intracellular delivery and nanotube-induced protection of siRNA from nuclease degradation. This study establishes that nanotubes, which are below the size exclusion limit of the plant cell wall, could enable a myriad of plant biotechnology applications that rely on RNA delivery. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/564427 doi: bioRxiv preprint Plants are central in providing over 25% of our most clinically-relevant drugs, are at the core of our sustainability efforts, and will benefit from genetic engineering to feed our growing population in the midst of climate change. Plant biotechnology is currently limited by the cost, ease, and throughput of methods for probing plant genetics and gene expression profiles. Consequently, less than a dozen complete biosynthetic pathways are known for plant natural products that have been reconstituted heterologously, compared to the ~1000 known biosynthetic pathways in bacteria and fungi 1 . RNA interference (RNAi) is sequence-specific inhibition of gene expression at the messenger RNA (mRNA) level, and can either consist of transcriptional gene silencing (TGS) or post-transcriptional gene silencing (PTGS). In PTGS, small RNA moleculesmicro (miRNA) or small interfering (siRNA)direct enzyme complexes to degrade mRNA molecules, hence suppress their activity by preventing translation.PTGS has shown to be a prominent tool in plants for genotype-phenotype mapping 2 , discovery of new biosynthetic pathways 3 , increased production of valuable small molecules 4,5 , understanding the functions of genes and proteins 6 , and to confer resistance to plant diseases 7,8 . One common way of utilizing PTGS in plants is to directly deliver siRNA molecules into cells. However, plants have a cell wall which presents a barrier to exogenous biomolecule delivery, whereby the plant cell wall size exclusion limit is ~ 5-20 nm 9 . Consequently, viral vectors combined with Agrobacterium tumefaciens delivery is the preferred method to deliver siRNA into intact plant cells. Viral vectors present the advantage of directly and strongly expressing the siRNA without relying on plant transformation, however, mos...

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Using Gold Nanoparticles as Delivery Vehicles for Targeted Delivery of Chemotherapy Drug Fludarabine Phosphate to Treat Hematological Cancers

Cited by 37 publications

References 0 publications

Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds

Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds

DNA Nanostructures Coordinate Gene Silencing in Mature Plants

Nanotubes effectively deliver siRNA to intact plant cells and protect siRNA against nuclease degradation

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