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WIREs Nanomed Nanobiotechnol
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Challenges in the development of nanoparticle‐based imaging agents: Characterization and biology

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Abstract Despite imaging agents being some of the earliest nanomedicines in clinical use, the vast majority of current research and translational activities in the nanomedicine field involves therapeutics, while imaging agents are severely underrepresented. The reasons for this lack of representation are several fold, including difficulties in synthesis and scale‐up, biocompatibility issues, lack of suitable tissue/disease selective targeting ligands and receptors, and a high bar for regulatory approval. The recent focus on immunotherapies and personalized medicine, and development of nanoparticle constructs with better tissue distribution and selectivity, provide new opportunities for nanomedicine imaging agent development. This manuscript will provide an overview of trends in imaging nanomedicine characterization and biocompatibility, and new horizons for future development. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
NIH‐sponsored grant proposals (applications) for nano‐enabled imaging applications. (a) Comparisons between the number of imaging agent applications versus all applications submitted to the nanotechnology FOAs between 2005 and 2019. Data were extracted from the NIH and NCI nanotechnology FOAs referenced in the main text. Imaging agent applications were defined as applications with keywords “imaging agent” or “imaging probe” in the titles or abstracts. (b) Additional breakdown of the imaging agent applications and awards. The outermost ring depicts the type of applications received. The series of inner rings highlight the focus of those applications that were awarded, whereby research grants with a cancer focus using optical/fluorescent imaging were predominant
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Peptide signatures from in vitro, in vivo and ex vivo screens of various cells and tissues. Using PHASTpep, a matrix was generated with normalized frequencies of various peptides (rows) across various screens (columns). PHASTpep normalizes each screen to its read depth and an amplified, unselected library, and generates matrix where each row represents a unique peptide sequence and each column is a positive and negative screen. This matrix can be sorted to display ideal peptide sequences specific for a cell, protein or organ, which helps narrow down peptide sequences for further validation. This sorted matrix can be represented as heat map, as shown here, which helps to identify the specificity of any peptide across various screens/targets. B, B‐cells; CHO, Chinese hamster ovary; Eff, effector; gl, glucose; Ob, obese; Omm, ommental; PDEC, pancreatic ductal epithelial cell; SVF, stromal vascular fraction; TIL, tumor infiltrating lymphocyte (Reprinted with permission from Brinton et al. (2016). Copyright 2016 PLoS)
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The ideal imaging nanoparticle will avoid the MPS (liver), rapidly accumulate in target tissue by receptor‐mediated transcytosis or passive/active targeting mechanisms, and undergo renal elimination to increase signal/background
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Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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