New views on cellular uptake and trafficking of manufactured nanoparticles

Treuel, Lennart; Jiang, Xiue; Nienhaus, G. Ulrich

doi:10.1098/rsif.2012.0939

Cited by 315 publications

(243 citation statements)

References 114 publications

Supporting

Mentioning

231

Contrasting

Unclassified

Order By: Relevance

“…High-Z nanoparticles (NPs) have been shown to improve the effectiveness of dose conformity to tumour tissue in the case of conventional unsegmented kilovoltage X-rays [19][20][21][22][23][24][25][26][27][28][29][30]. The advantages of NPs, besides the primary benefit of enhancing tumour radiosensitivity, often include biocompatibility, permeability to cell membranes due to their nano-scale dimensions, ability to specifically target certain tumours when coated and actively accumulate at tumour sites with leaky vasculature [21,22].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

et al. 2016

View full text Add to dashboard Cite

Microbeam Radiation Therapy (MRT) exploits tumour selectivity and normal tissue sparing with spatially fractionated kilovoltage X-ray microbeams through the dose volume effect. Experimental measurements with Ta 2 O 5 nanoparticles (NPs) in 9L gliosarcoma treated with MRT at the Australian Synchrotron, increased the treatment efficiency. Ta 2 O 5 NPs were observed to form shells around cell nuclei which may be the reason for their efficiency in MRT. In this article, our experimental observation of NP shell formation is the basis of a Geant4 radiation transport study to characterise dose enhancement by Ta 2 O 5 NPs in MRT. Our study showed that NP shells enhance the physical dose depending microbeam energy and their location relative to a single microbeam. For monochromatic microbeam energies below ∼70 keV, NP shells show highly localised dose enhancement due to the short range of associated secondary electrons. Low microbeam energies indicate better targeted treatment by allowing higher microbeam doses to be administered to tumours and better exploit the spatial fractionation related selectivity observed with MRT. For microbeam energies above ∼100 keV, NP shells extend the physical dose enhancement due to longer-range secondary electrons. Again, with NPs selectively internalised, the local effectiveness of MRT is expected to increase in the tumour. Dose enhancement produced by the shell aggregate varied more significantly in the cell population, depending on its location, when compared to a homogeneous NP distribution. These combined simulation and experimental data provide first evidence for optimising MRT through the incorporation of newly observed Ta 2 O 5 NP distributions within 9L cancer cells. Disciplines Engineering | Science and Technology Studies Publication DetailsEngels, E., Corde, S., McKinnon, S., Incerti, S., Konstantinov, K., Rozenfeld, A., Tehei, M., . Optimizing dose enhancement with Ta2O5 nanoparticles for synchrotron microbeam activated radiation therapy. Physica Medica: an international journal devoted to the applications of physics to medicine and biology, 32 (12)

show abstract

Section: Introductionmentioning

confidence: 99%

“…The advantages of NPs, besides the primary benefit of enhancing tumour radiosensitivity, often include biocompatibility, permeability to cell membranes due to their nano-scale dimensions, ability to specifically target certain tumours when coated and actively accumulate at tumour sites with leaky vasculature [21,22].…”

Section: Introductionmentioning

confidence: 99%

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Despite the potential of nanomaterials, typically less than 5% of an administered dose reaches the tumor compartment (6) because of poor retention within the tumor space and uptake by the skin (7), spleen, and liver (8)(9)(10). Refinements to the size, shape, and surface chemistry of nanomaterials have improved their blood half-lives (11,12) and interactions with cancer cells (13)(14)(15). Unfortunately, clinical translation of cancer nanomedicine remains stagnated by adherence to the ideology that nanoparticles and other agents can be designed to "universally" detect and treat tumors independent of type or stage of cancer progression.…”

mentioning

confidence: 99%

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

Sykes

Dai

Sarsons

et al. 2016

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

248

163

View full text Add to dashboard Cite

Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient's disease state to achieve optimal diagnostic and therapeutic outcomes.cancer | nanoparticles | targeting | nano-bio interactions | tumor

show abstract

“…For most particle types, the default pathway following internalization is to lysosomes [91,92] Fluorescence-based imaging has made a major contributor to this observation, with many studies using colocalization of particles with fluorescent markers of lysosomes (e.g., LysoTracker®, or immunostaining with lysosomal proteins, such as LAMP1) [93,94]. Therefore, the spatial and temporal resolution offered by fluorescence microscopy provides quantitative data relating to the organelles through which NPs pass en route to the lysosomes.…”

Section: Hca: Detailed Mechanisms Of Np Internalization and Intracellmentioning

confidence: 99%

High-content analysis for drug delivery and nanoparticle applications

Brayden

Cryan

Dawson

et al. 2015

Drug Discovery Today

View full text Add to dashboard Cite

Publication information Drug Discovery Today, 20 (8): 942-957Publisher Elsevier Item record/more information http://hdl.handle.net/10197/6636 Publisher's statementThis is the author's version of a work that was accepted for publication in Drug Discovery Today. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Drug Discovery Today, 20 (8), (2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 26A c c e p t e d M a n u s c r i p t Sally-Ann CryanSally-Ann Cryan has a pharmacy degree and a PhD in pharmaceutics ( Jeremy SimpsonJeremy Simpson carried out his PhD at the University of Warwick, followed postdoctoral work at the Scripps Research Institute in San Diego, and the Imperial Cancer Research Fund in London. After 9 years as a staff member at the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany), he was appointed as professor of cell biology at UCD, in 2008. He currently applies high-throughput imaging technologies to study subcellular transport pathways and the internalization routes taken by nanoparticles in cells. He runs the UCD Cell Screening Laboratory and is the author of more than 80 publications.High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents. A brief recap of cytotoxicity assaysIn vitro cell-based assays have long been used to assess the cytotoxic effects of drug exposure [1]. Cells undergoing acute necrosis swell and lose metabolic capacity, thereby losing the capacity to maintain a barrier to the extracellular space and the ability ...

show abstract

New views on cellular uptake and trafficking of manufactured nanoparticles

Cited by 315 publications

References 114 publications

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

High-content analysis for drug delivery and nanoparticle applications

Contact Info

Product

Resources

About