Common pitfalls in nanotechnology: lessons learned from NCI's Nanotechnology Characterization Laboratory

Crist, Rachael M.; Grossman, Jennifer; Patri, Anil K.; Stern, Stęphan T.; Dobrovolskaia, Marina A.; Adiseshaiah, Pavan P.; Clogston, Jeffrey D.; McNeil, Scott E.

doi:10.1039/c2ib20117h

Cited by 222 publications

(214 citation statements)

References 34 publications

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“…Reliable measurements of nanocarrier disassembly additionally are hampered by the time and sample manipulations required for analysis, adversely affecting the accuracy of available techniques (11). The development of novel approaches enabling continuous, noninvasive monitoring of NP disassembly directly in living cells, as well as in environments modeling exposure to various types of biological milieu, may inform the design and optimization of biodegradable NP formulations for a wide range of biomedical applications and facilitate their translation into the clinic (12).…”

mentioning

confidence: 99%

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

Tengood

Alferiev

Zhang

et al. 2014

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

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The fate of nanoparticle (NP) formulations in the multifaceted biological environment is a key determinant of their biocompatibility and therapeutic performance. An understanding of the degradation patterns of different types of clinically used and experimental NP formulations is currently incomplete, posing an unmet need for novel analytical tools providing unbiased quantitative measurements of NP disassembly directly in the medium of interest and in conditions relevant to specific therapeutic/ diagnostic applications. In the present study, this challenge was addressed with an approach enabling real-time in situ monitoring of the integrity status of NPs in cells and biomimetic media using Förster resonance energy transfer (FRET). Disassembly of polylactidebased magnetic NPs (MNPs) was investigated in a range of model biomimetic media and in cultured vascular cells using an experimentally established quantitative correlation between particle integrity and FRET efficiency controlled through adjustments in the spectral overlap between two custom-synthesized polylactide-fluorophore (boron dipyrromethene) conjugates incorporated in MNPs. The results suggest particle disassembly governed by diffusion-reaction processes with kinetics strongly dependent on conditions promoting release of oligomeric fragments from the particle matrix. Thus, incubation in gels simulating the extracellular environment and in protein-rich serum resulted in notably lower and higher MNP decomposition rates, respectively, compared with nonviscous liquid buffers. The diffusion-reaction mechanism also is consistent with a significant cell growth-dependent acceleration of MNP processing in dividing vs. contact-inhibited vascular cells. The FRET-based analytical strategy and experimental results reported herein may facilitate the development and inform optimization of biodegradable nanocarriers for cell and drug delivery applications.nanoparticle degradation | direct assay | endothelial cell | smooth muscle cell | restenosis N anoparticles (NPs) of different compositions and designs are emerging as versatile diagnostic tools and promising carriers for delivery of small molecule drugs and biotherapeutics (1, 2). Among the prerequisites for their safe and effective use, an understanding of the fate of NPs intended for diagnostic or therapeutic applications is an obvious requirement, as it ensures the absence of acute or chronic toxicity caused by foreign materials retained in the body (3). Biodegradation of NPs developed as drug delivery carriers also plays a key role in their therapeutic performance by contributing to the biodistribution and fate of the cargo; thus, it is of essential importance for optimizing the site specificity and duration of the pharmacological effect for a given application (4).Despite the recognized need for definitive studies of NP degradation and factors governing its kinetics (5), investigative strategies providing reliable in situ measurements of NP disassembly are lacking. The few in vitro studies examining the stabili...

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mentioning

confidence: 99%

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

Tengood

Alferiev

Zhang

et al. 2014

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

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“…Efforts to elucidate how best to optimize NPs for specific tasks comprise much of the basic science of these NPs. Organizations such as the National Cancer Institute's Nanotechnology Characterization Laboratory have played important roles in guiding such efforts (70). Although approved clinical applications are beginning to appear, the bulk of the science is still maturing through mouse model studies.…”

Section: Inorganic Nanoparticles and Related Nanomaterials In Biomedimentioning

confidence: 99%

Nanotechnologies for biomedical science and translational medicine

Heath

2015

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

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In 2000 the United States launched the National Nanotechnology Initiative and, along with it, a well-defined set of goals for nanomedicine. This Perspective looks back at the progress made toward those goals, within the context of the changing landscape in biomedicine that has occurred over the past 15 years, and considers advances that are likely to occur during the next decade. In particular, nanotechnologies for health-related genomics and single-cell biology, inorganic and organic nanoparticles for biomedicine, and wearable nanotechnologies for wellness monitoring are briefly covered.nanotechnology | biotechnology | nanomedicine

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“…Nanomedicine characterization can be divided in three steps: first, an analytical characterization, useful for characterizing the materials they are composed of as well as to find out the impurities present and develop purification processes; second, a physicochemical characterization of the main parameters that will define the performance of nanomaterials in vivo, such as size, surface charge, and stability in biological conditions; and third, the study of their interaction with biological components (Figure 1). Although many reviews for the characterization of polymeric nanoparticles designed as nanomedicines exist, most of them give a particular point of view, signaling only some techniques [2,5,6]. Therefore, scientists working on the development of novel nanoformulations find themselves lost in the huge but dispersed existent bibliography.…”

Section: Introductionmentioning

confidence: 99%

Analytical Methods to Characterize and Purify Polymeric Nanoparticles

Fornaguera

Solans

2018

International Journal of Polymer Science

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Advances in polymeric nanoparticles as novel nanomedicines have opened a new class of diagnostic and therapeutic tools for many diseases. However, although the benchtop research studies in the nanoworld are numerous, their translation to currently marketed products is still limited. This lack of transference can be attributed, among other factors, to problems with nanomedicine characterization. Characterization techniques at the nanoscale could be divided in three categories: characterization of physicochemical properties (e.g., size and surface charge), characterization of nanomaterials interactions with biological components (e.g., proteins from the blood), and analytical characterization and purification methods. Currently available literature of this last group only describes methodologies applied for a specific type of nanomaterial or even methods used for bulk materials, which are not completely applicable to nanomaterials. For this reason, the current review aims to become a scholastic guide for those scientists starting in the nanoworld, giving them a description of analytical characterization techniques aimed to analyze polymers forming nanoparticles and possible forms to purify them before being used in preclinical and clinical applications.

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Common pitfalls in nanotechnology: lessons learned from NCI's Nanotechnology Characterization Laboratory

Cited by 222 publications

References 34 publications

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

Nanotechnologies for biomedical science and translational medicine

Analytical Methods to Characterize and Purify Polymeric Nanoparticles

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