Publications by authors named "Richard A Revia"

10 Publications

  • Page 1 of 1

Iron oxide nanoparticles for immune cell labeling and cancer immunotherapy.

Nanoscale Horiz 2021 Jul 20. Epub 2021 Jul 20.

Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.

Cancer immunotherapy is a novel approach to cancer treatment that leverages components of the immune system as opposed to chemotherapeutics or radiation. Cell migration is an integral process in a therapeutic immune response, and the ability to track and image the migration of immune cells in vivo allows for better characterization of the disease and monitoring of the therapeutic outcomes. Iron oxide nanoparticles (IONPs) are promising candidates for use in immunotherapy as they are biocompatible, have flexible surface chemistry, and display magnetic properties that may be used in contrast-enhanced magnetic resonance imaging (MRI). In this review, advances in application of IONPs in cell tracking and cancer immunotherapy are presented. Following a brief overview of the cancer immunity cycle, developments in labeling and tracking various immune cells using IONPs are highlighted. We also discuss factors that influence the effectiveness of IONPs as MRI contrast agents. Finally, we outline different approaches for cancer immunotherapy and highlight current efforts that utilize IONPs to stimulate immune cells to enhance their activity and response to cancer.
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http://dx.doi.org/10.1039/d1nh00179eDOI Listing
July 2021

Microfluidic Synthesis of Iron Oxide Nanoparticles.

Nanomaterials (Basel) 2020 Oct 23;10(11). Epub 2020 Oct 23.

Department of Materials Science and Engineering, University of Washington, Seattle, WA 98105, USA.

Research efforts into the production and application of iron oxide nanoparticles (IONPs) in recent decades have shown IONPs to be promising for a range of biomedical applications. Many synthesis techniques have been developed to produce high-quality IONPs that are safe for in vivo environments while also being able to perform useful biological functions. Among them, coprecipitation is the most commonly used method but has several limitations such as polydisperse IONPs, long synthesis times, and batch-to-batch variations. Recent efforts at addressing these limitations have led to the development of microfluidic devices that can make IONPs of much-improved quality. Here, we review recent advances in the development of microfluidic devices for the synthesis of IONPs by coprecipitation. We discuss the main architectures used in microfluidic device design and highlight the most prominent manufacturing methods and materials used to construct these microfluidic devices. Finally, we discuss the benefits that microfluidics can offer to the coprecipitation synthesis process including the ability to better control various synthesis parameters and produce IONPs with high production rates.
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http://dx.doi.org/10.3390/nano10112113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690813PMC
October 2020

Graphene Quantum Dots and Their Applications in Bioimaging, Biosensing, and Therapy.

Adv Mater 2021 Jun 12;33(22):e1904362. Epub 2019 Dec 12.

Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.

Graphene quantum dots (GQDs) are carbon-based, nanoscale particles that exhibit excellent chemical, physical, and biological properties that allow them to excel in a wide range of applications in nanomedicine. The unique electronic structure of GQDs confers functional attributes onto these nanomaterials such as strong and tunable photoluminescence for use in fluorescence bioimaging and biosensing, a high loading capacity of aromatic compounds for small-molecule drug delivery, and the ability to absorb incident radiation for use in the cancer-killing techniques of photothermal and photodynamic therapy. Recent advances in the development of GQDs as novel, multifunctional biomaterials are presented with a focus on their physicochemical, electronic, magnetic, and biological properties, along with a discussion of technical progress in the synthesis of GQDs. Progress toward the application of GQDs in bioimaging, biosensing, and therapy is reviewed, along with a discussion of the current limitations and future directions of this exciting material.
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http://dx.doi.org/10.1002/adma.201904362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289657PMC
June 2021

A Portable Electrospinner for Nanofiber Synthesis and Its Application for Cosmetic Treatment of Alopecia.

Nanomaterials (Basel) 2019 Sep 14;9(9). Epub 2019 Sep 14.

Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.

A portable, handheld electrospinning apparatus is designed and constructed using off-the-shelf components and 3D-printed parts. The portable electrospinner is used to generate nanofibers with diameters ranging from 85 to 600 nm; examination of these fibers is achieved with scanning electron microscopy. This portable electrospinner has similar capabilities to standard stationary benchtop electrospinners in terms of the diversity of polymers the device is able to spin into nanofibers and their resulting size and morphology. However, it provides much more ambulatory flexibility, employs current-limiting measures that allow for safer operation and is cost effective. As a demonstration of the device's unique application space afforded by its portability, the device is applied in direct-to-skin electrospinning to improve the aesthetics of simulated hair loss in a mouse model by electrospinning dyed polyacrylonitrile nanofibers that mimic hair. The superficial nanofiber treatment for thinning hair is able to achieve an improvement in appearance similar to that of a commercially available powder product but outperforms the powder in the nanofiber's superior adherence to the affected area. The portable electrospinning apparatus overcomes many limitations of immobile benchtop electrospinners and holds promise for applications in consumer end-use scenarios such as the treatment of alopecia via cosmetic hair thickening.
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http://dx.doi.org/10.3390/nano9091317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781269PMC
September 2019

Nitrogen and Boron Dual-Doped Graphene Quantum Dots for Near-Infrared Second Window Imaging and Photothermal Therapy.

Appl Mater Today 2019 Mar 6;14:108-117. Epub 2018 Dec 6.

Department of Materials Science and Engineering, University of Washington, Seattle 98195, United States.

Fluorescence imaging of biological systems in the second near-infrared window (NIR-II) has recently drawn much attention because of its negligible background noise of autofluorescence and low tissue scattering. Here we present a new NIR-II fluorescent agent, graphene quantum dots dual-doped with both nitrogen and boron (N-B-GQDs). N-B-GQDs have an ultra-small size (~ 5 nm), are highly stable in serum, and demonstrate a peak fluorescent emission at 1000 nm and high photostability. In addition to the NIR-II imaging capability, N-B-GQDs efficiently absorb and convert NIR light into heat when irradiated by an external NIR source, demonstrating a photothermal therapeutic effect that kills cancer cells in vitro and completely suppresses tumor growth in a glioma xenograft mouse model. N-B-GQDs demonstrate a safe profile, prolonged blood half-life, and rapid excretion in mice, which are the characteristics favorable for in vivo biomedical applications.
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http://dx.doi.org/10.1016/j.apmt.2018.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752708PMC
March 2019

Time-Resolved MRI Assessment of Convection-Enhanced Delivery by Targeted and Nontargeted Nanoparticles in a Human Glioblastoma Mouse Model.

Cancer Res 2019 09 22;79(18):4776-4786. Epub 2019 Jul 22.

Department of Materials Science and Engineering, University of Washington, Seattle, Washington.

Convection-enhanced delivery (CED) provides direct access of infusates to brain tumors; however, clinical translation of this technology has not been realized because of the inability to accurately visualize infusates in real-time and lack of targeting modalities against diffuse cancer cells. In this study, we use time-resolved MRI to reveal the kinetics of CED processes in a glioblastoma (GBM) model using iron oxide nanoparticles (NP) modified with a glioma-targeting ligand, chlorotoxin (CTX). Mice bearing orthotopic human GBM tumors were administered a single dose of targeted CTX-conjugated NP (NPCP-CTX) or nontargeted NP (NPCP) via CED. High-resolution T2-weighted, T2*-weighted, and quantitative T2 MRI were utilized to image NP delivery in real time and determined the volume of distribution (V) of NPs at multiple time points over the first 48 hours post-CED. GBM-specific targeting was evaluated by flow cytometry and intracellular NP localization by histologic assessment. NPCP-CTX produced a V of 121 ± 39 mm at 24 hours, a significant increase compared with NPCP, while exhibiting GBM specificity and localization to cell nuclei. Notably, CED of NPCP-CTX resulted in a sustained expansion of V well after infusion, suggesting a possible active transport mechanism, which was further supported by the presence of NPs in endothelial and red blood cells. In summary, we show that time-resolved MRI is a suitable modality to study CED kinetics, and CTX-mediated CED facilitates extensive distribution of infusate and specific targeting of tumor cells. SIGNIFICANCE: MRI is used to monitor convection-enhanced delivery in real time using a nanoparticle-based contrast agent, and glioma-specific targeting significantly improves the volume of distribution in tumors.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744959PMC
September 2019

Theranostic Nanoparticles for RNA-Based Cancer Treatment.

Acc Chem Res 2019 06 28;52(6):1496-1506. Epub 2019 May 28.

Department of Materials Science and Engineering , University of Washington , Seattle , Washington 98195 , United States.

Certain genetic mutations lead to the development of cancer through unchecked cell growth and division. Cancer is typically treated through surgical resection, radiotherapy, and small-molecule chemotherapy. A relatively recent approach to cancer therapy involves the use of a natural process wherein small RNA molecules regulate gene expression in a pathway known as RNA interference (RNAi). RNA oligomers pair with a network of proteins to form an RNA-induced silencing complex, which inhibits the translation of mRNA into proteins, thereby controlling the expression of gene products. Synthetically produced RNA oligomers may be designed to target and silence specific oncogenes to provide cancer therapy. The primary challenges facing the use of the RNAi pathway for cancer therapy are the safe and efficacious delivery of RNA payloads and their release at pertinent sites within disease-causing cells. Nucleases are abundant in the bloodstream and intracellular environment, and therapeutic RNA sequences often require a suitable carrier to provide protection from degradation prior to reaching their site of action in the body. The use of metal core nanoparticles (NPs) serving as targeted delivery vehicles able to shield and direct RNA payloads to their intended destinations have recently gained favor. Biological barriers present in the body establish a size prerequisite for drug delivery vehicles; to overcome recognition by the body's immune system and to gain access to intracellular environments, drug carriers must be small (< 100 nm). Iron oxide and gold core NPs can be synthesized with a high degree of control to create uniform ultrasmall drug delivery vehicles capable of bypassing key biological barriers. While progress is being made in size control of liposomal and polymer NPs, such advances still lag in comparison to the exquisite tunability and time stability of size engineering achievable with metal core NPs at bulk scales. Further, unlike lipid- and viral-based transfection agents, the biodistribution of metal core NPs can be traced using noninvasive imaging techniques that capitalize on the interaction of electromagnetic radiation and the inorganic atoms at the core of the NPs. Finally, metal core NPs have been shown to match the transfection efficiency of conventional RNA-delivery vehicles while also providing less immunogenicity and minimal side effects through the addition of tumor-targeting ligands on their surface. This Account reviews recent advances in the use of iron oxide and gold NPs for RNAi therapy. An overview of the different types of RNA-based therapies is provided along with a discussion of the advantages and current limitations of the technique. We highlight design considerations for the use of iron oxide and gold NP carriers in RNAi, including a discussion of the importance of size and its role in traversing biological barriers, NP surface modifications required for targeted delivery and RNA payload release, and auxiliary properties supporting imaging functionality for treatment monitoring. Applications of NPs for combination therapies including the pairing of RNAi with chemotherapy, photothermal therapy, immunotherapy, and radiotherapy are explored through examples. Finally, future perspectives are provided with a focus on the current limitations and the potential for clinical translation of iron oxide and gold NPs in RNAi therapy.
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http://dx.doi.org/10.1021/acs.accounts.9b00101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701180PMC
June 2019

Nanoparticle Biokinetics in Mice and Nonhuman Primates.

ACS Nano 2017 09 18;11(9):9514-9524. Epub 2017 Sep 18.

Clinical Research Division, Fred Hutchinson Cancer Research Center , Seattle, Washington 98109, United States.

Despite the preponderance of iron oxide nanoparticles (NPs) designed for theranostic applications, widespread clinical translation of these NPs lags behind. A better understanding of how NP pharmacokinetics vary between small and large animal models is needed to rapidly customize NPs for optimal performance in humans. Here we use noninvasive magnetic resonance imaging (MRI) to track iron oxide NPs through a large number of organ systems in vivo to investigate NP biokinetics in both mice and nonhuman primates. We demonstrate that pharmacokinetics are similar between mice and macaques in the blood, liver, spleen, and muscle, but differ in the kidneys, brain, and bone marrow. Our study also demonstrates that full-body MRI is practical, rapid, and cost-effective for tracking NPs noninvasively with high spatiotemporal resolution. Our techniques using a nonhuman primate model may provide a platform for testing a range of NP formulations.
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http://dx.doi.org/10.1021/acsnano.7b05377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002853PMC
September 2017

Magnetite nanoparticles for cancer diagnosis, treatment, and treatment monitoring: recent advances.

Mater Today (Kidlington) 2016 Apr;19(3):157-168

Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.

The development of nanoparticles (NPs) for use in all facets of oncological disease detection and therapy has shown great progress over the past two decades. NPs have been tailored for use as contrast enhancement agents for imaging, drug delivery vehicles, and most recently as a therapeutic component in initiating tumor cell death in magnetic and photonic ablation therapies. Of the many possible core constituents of NPs, such as gold, silver, carbon nanotubes, fullerenes, manganese oxide, lipids, micelles, etc., iron oxide (or magnetite) based NPs have been extensively investigated due to their excellent superparamagnetic, biocompatible, and biodegradable properties. This review addresses recent applications of magnetite NPs in diagnosis, treatment, and treatment monitoring of cancer. Finally, some views will be discussed concerning the toxicity and clinical translation of iron oxide NPs and the future outlook of NP development to facilitate multiple therapies in a single formulation for cancer theranostics.
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http://dx.doi.org/10.1016/j.mattod.2015.08.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981486PMC
April 2016

Approach to Rapid Synthesis and Functionalization of Iron Oxide Nanoparticles for High Gene Transfection.

ACS Appl Mater Interfaces 2016 Mar 4;8(10):6320-8. Epub 2016 Mar 4.

Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.

Surface functionalization of theranostic nanoparticles (NPs) typically relies on lengthy, aqueous postsynthesis labeling chemistries that have limited ability to fine-tune surface properties and can lead to NP heterogeneity. The need for a rapid, simple synthesis approach that can provide great control over the display of functional moieties on NP surfaces has led to increased use of highly selective bioorthoganol chemistries including metal-affinity coordination. Here we report a simple approach for rapid production of a superparamagnetic iron oxide NPs (SPIONs) with tunable functionality and high reproducibility under aqueous conditions. We utilize the high affinity complex formed between catechol and Fe((III)) as a means to dock well-defined catechol modified polymer modules on the surface of SPIONs during sonochemical coprecipitation synthesis. Polymer modules consisted of chitosan and poly(ethylene glycol) (PEG) copolymer (CP) modified with catechol (CCP), and CCP functionalized with cationic polyethylenimine (CCP-PEI) to facilitate binding and delivery of DNA for gene therapy. This rapid synthesis/functionalization approach provided excellent control over the extent of PEI labeling, improved SPION magnetic resonance imaging (MRI) contrast enhancement and produced an efficient transfection agent.
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http://dx.doi.org/10.1021/acsami.5b10883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829641PMC
March 2016
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