Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body 18 F-fluodeoxyglucose positron emission tomography ([ 18 F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [ 18 F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high glucose uptake. We have developed a PET imaging strategy for DLBCL that targets poly[ADP ribose] polymerase 1 (PARP1), the expression of which has been found to be much higher in DLBCL than in healthy tissues. In a syngeneic DLBCL mouse model, this PARP1-targeted PET imaging approach allowed us to discriminate between malignant and inflamed lymph nodes, whereas [ 18 F]FDG-PET failed to do so. Our PARP1-targeted PET imaging approach may be an attractive addition to the current PET imaging strategy to differentiate inflammation from malignancy in DLBCL.PET/CT | PARP1 | [ 18 F]PARPi | diffuse large B-cell lymphoma | inflammation

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“…Previously established protocols were adapted to analyze the tissues in this study (53). In brief, at 2.5 h after i.v.…”

Section: Methodsmentioning

confidence: 99%

Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma

Tang

Salloum

Carney

et al. 2017

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

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“…This procedure serves as a backbone to build specific experiments to characterize cancer nanomedicines for different applications. For example, researchers can determine quantitative in vivo pharmacokinetics of the nanomaterial when PET-CT scans are performed at multiple time points on the same animals 17 ; they can collect biodistribution information of the nanomaterials by analyzing other tissues, such as the large intestines, small intestines, pancreas, brain, skin, thymus, stomach, or salivary glands, as shown in other publications 18, 19, 20, 21 ; or they can evaluate the single-cell and subcellular specificity of nanomedicines in relevant tissues other than tumors by applying this flow cytometry and immunostaining protocol.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Procedure to Evaluate the <em>In Vivo</em> Performance of Cancer Nanomedicines

Tang

Pérez-Medina

Zhao

et al. 2017

JoVE

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Inspired by the success of previous cancer nanomedicines in the clinic, researchers have generated a large number of novel formulations in the past decade. However, only a small number of nanomedicines have been approved for clinical use, whereas the majority of nanomedicines under clinical development have produced disappointing results. One major obstacle to the successful clinical translation of new cancer nanomedicines is the lack of an accurate understanding of their in vivo performance. This article features a rigorous procedure to characterize the in vivo behavior of nanomedicines in tumor-bearing mice at systemic, tissue, single-cell, and subcellular levels via the integration of positron emission tomography-computed tomography (PET-CT), radioactivity quantification methods, flow cytometry, and fluorescence microscopy. Using this approach, researchers can accurately evaluate novel nanoscale formulations in relevant mouse models of cancer. These protocols may have the ability to identify the most promising cancer nanomedicines with high translational potential or to aid in the optimization of cancer nanomedicines for future translation.

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“…Implementing screening procedures to evaluate new and preexisting nanomaterials with regards to their compatibility with different drugs, their biological behavior and tissue/cell specificity and their toxicity profile is the key to developing clinically relevant nanotherapeutics and diagnostic agents[272–274]. …”

Section: Lessons Challenges and Perspectivesmentioning

confidence: 99%

Applying nanomedicine in maladaptive inflammation and angiogenesis

Alaarg

Pérez-Medina

Metselaar

et al. 2017

Advanced Drug Delivery Reviews

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Inflammation and angiogenesis drive the development and progression of multiple devastating diseases such as atherosclerosis, cancer, rheumatoid arthritis, and inflammatory bowel disease. Though these diseases have very different phenotypic consequences, they possess several common pathophysiological features in which monocyte recruitment, macrophage polarization, and enhanced vascular permeability play critical roles. Thus, developing rational targeting strategies tailored to the different stages of the journey of monocytes, from bone marrow to local lesions, and their extravasation from the vasculature in diseased tissues will advance nanomedicine. The integration of in vivo imaging uniquely allows studying nanoparticle kinetics, accumulation, clearance, and biological activity, at levels ranging from subcellular to an entire organism, and will shed light on the fate of intravenously administered nanomedicines. We anticipate that convergence of nanomedicines, biomedical engineering, and life sciences will help to advance clinically relevant therapeutics and diagnostic agents for patients with chronic inflammatory diseases.

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Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Cited by 106 publications

References 48 publications

Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma

Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma

A Comprehensive Procedure to Evaluate the <em>In Vivo</em> Performance of Cancer Nanomedicines

Applying nanomedicine in maladaptive inflammation and angiogenesis

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