Big Potential from Small Agents: Nanoparticles for Imaging-Based Companion Diagnostics

Ehlerding, Emily B.; Grodzinski, Piotr; Cai, Weibo; Liu, Christina

doi:10.1021/acsnano.7b07252

Cited by 126 publications

(92 citation statements)

References 195 publications

(355 reference statements)

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“…A general scheme for the one-pot polyol synthesis of the PMVEMA-coated ultra-small Gd 2 O 3 NPs is shown in Figure 8. Three separate solutions were prepared: 1 (2) was slowly added to solution (1) and the resulting mixture solution was magnetically stirred for 30 min. The solution (3) was then slowly added to the aforementioned mixture solution until the pH of the solution reached~10.…”

Section: Methodsmentioning

confidence: 99%

“…Nanoparticle (NP) imaging agents have attracted much attention because of their advanced imaging properties compared with those of conventional molecular agents [1][2][3][4][5][6]. In addition, NPs can deliver various functional materials such as drugs for advanced applications that exploit their large specific surface areas [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles

Ahmad

Yue

et al. 2020

Molecules

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The study of ultra-small paramagnetic gadolinium oxide (Gd2O3) nanoparticles (NPs) as in vivo positive (T1) magnetic resonance imaging (MRI) contrast agents is one of the most attractive fields in nanomedicine. The performance of the Gd2O3 NP imaging agents depends on the surface-coating materials. In this study, poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was used as a surface-coating polymer. The PMVEMA-coated paramagnetic ultra-small Gd2O3 NPs with an average particle diameter of 1.9 nm were synthesized using the one-pot polyol method. They exhibited excellent colloidal stability in water and good biocompatibility. They also showed a very high longitudinal water proton spin relaxivity (r1) value of 36.2 s−1mM−1 (r2/r1 = 2.0; r2 = transverse water proton spin relaxivity) under a 3.0 tesla MR field which is approximately 10 times higher than the r1 values of commercial molecular contrast agents. High positive contrast enhancements were observed in in vivo T1 MR images after intravenous administration of the NP solution sample, demonstrating its potential as a T1 MRI contrast agent.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles

Ahmad

Yue

et al. 2020

Molecules

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“…This could be achieved through identifying "niche" applications which are uniquely positioned to benefit from nanotechnology and do not have viable contemporary solutions, expanding the scope of monotherapies to combination therapies delivering two or more synergistic drugs and/or engaging more than one treatment modalities. These strategies can be further facilitated by the implementation of companion diagnostics relying on testing the strength of the Enhanced Permeability and Retention (EPR) effect responsible for nanoparticle accumulation in solid tumors, and resulting in identification of patients for whom nanomedicines may be most effective (Ehlerding, Grodzinski, Cai, & Liu, 2018;Keating et al, 2018;Lee et al, 2017;Miller et al, 2015;Wong, Siah, & Lo, 2018). F I G U R E 1 1 The initial NCI funding and additional funding leveraged by funding to four Alliance CCNEs, which have been funded for all Phases of the program (California Institute of Technology, Northwestern University, Stanford University, and University of North Carolina at Chapel Hill).…”

Section: Discussionmentioning

confidence: 99%

National Cancer Institute Alliance for nanotechnology in cancer—Catalyzing research and translation toward novel cancer diagnostics and therapeutics

Hartshorn

Russell

Grodzinski

2019

WIREs Nanomed Nanobiotechnol

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Nanotechnology has been a burgeoning research field, which is finding compelling applications in several practical areas of everyday life. It has provided novel, paradigm shifting solutions to medical problems and particularly to cancer. In order to accelerate integration of nanotechnology into cancer research and oncology, the National Cancer Institute (NCI) of the National Institutes of Health (NIH) established the NCI Alliance for Nanotechnology in Cancer program in 2005. This effort brought together scientists representing physical sciences, chemistry, and engineering working at the nanoscale with biologists and clinicians working on cancer to form a uniquely multidisciplinary cancer nanotechnology research community. The last 14 years of the program have produced a remarkable body of scientific discovery and demonstrated its utility to the development of practical cancer interventions. This paper takes stock of how the Alliance program influenced melding of disparate research disciplines into the field of nanomedicine and cancer nanotechnology, has been highly productive in the scientific arena, and produced a mechanism of seamless transfer of novel technologies developed in academia to the clinical and commercial space. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging

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“…All X-ray images were processed, and image intensities quantified using ImageJ (NIH) normalized to unmodified polymer. (2); Typical Procedure. To a flame dried round bottom flask equipped with a stir bar was added 4-iodo-L-phenylalanine (17.2 mmol, 5.0 g, 1.0 equiv) and 0.5 M aq.…”

Section: Methodsmentioning

confidence: 99%

Iodinated Polyesters with Enhanced X-ray Contrast Properties for Biomedical Imaging

Lex

Brummel

Attia

et al. 2020

Sci Rep

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Synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. However, polymeric biomaterials are lacking imaging contrast properties for deep tissue imaging. this report details the synthesis and characterization of a suite of aryl-iodo monomers, which were used to prepare iodinated polyesters using a pre-functionalization approach. commercially available 4-iodo-phenylalanine or 4-iodobenzyl bromide served as the starting materials for the synthesis of three iodinated monomeric moieties (a modified lactide, morpholine-2,5-dione, and caprolactone), which under a tin-mediated ring-opening polymerization (Rop), generated their respective polyesters (pe) or poly(ester amides) (peA). An increase in X-ray intensity of all synthesized iodine-containing polymers, in comparison to non-iodinated poly(lactic acid) (pLA), validated their functionality as radio-opaque materials. the iodinated-poly(lactic acid) (ipLA) material was visualized through varying thicknesses of chicken tissue, thus demonstrating its potenial as a radio-opaque biomaterial. Medical imaging, a technique that provides structural visualization inside the body, aides in the study of specific morphological changes within living and nonliving systems 1,2. One particular imaging modality, X-ray radiography, is frequently used as a diagnostic tool for non-invasive, in vivo, real-time examinations of three-dimensional opaque objects. X-ray imaging can be used to monitor response, degradation, and defects of biomedical devices 3. Concerns over the long-term stability of prolonged or permanent implantable devices have led to the development of polyester-based materials due to their desirable properties (i.e. biocompatibility, biodegradability, and facile synthesis) 4-8. The evolution of biodegradable polyester devices, like staples, stents, sutures, and implants, have had a significant impact on the biomedical field 4,9,10. Perhaps the most noteworthy advantage is their ability to be degraded and excreted from the body, obviating the need for their removal or surgical revision. This can be vital in major surgical procedures such as fracture fixation, spinal fixation, and abdominal wall repair 4,10. While commercially available polyester devices have seen a considerable amount of use in the biomedical field, their in vivo performance can be difficult to predict and evaluate due to the complex biological environment associated with tissues 10,11. Therefore, the real-time monitoring of these devices is critical in order to understand their performance and fate in the body. The major drawback of polyester-based devices is that they lack inherent contrast imaging properties, making it difficult to visualize the area of interest. Imaging techniques are useful only when the intensity of a signal is sufficient enough to distinguish the target from surrounding tissues or materials. This issue becomes even more evident when imaging materials through deep tissue or when monitoring minor defects in biomaterials 12. Recent ...

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Big Potential from Small Agents: Nanoparticles for Imaging-Based Companion Diagnostics

Cited by 126 publications

References 195 publications

In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles

In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles

National Cancer Institute Alliance for nanotechnology in cancer—Catalyzing research and translation toward novel cancer diagnostics and therapeutics

Iodinated Polyesters with Enhanced X-ray Contrast Properties for Biomedical Imaging

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