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Article ; Online: An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria.

Lubkowicz, David / Horvath, Nicholas G / James, Michael J / Cantarella, Pasquale / Renaud, Lauren / Bergeron, Christopher G / Shmueli, Ron B / Anderson, Cami / Gao, Jian-Rong / Kurtz, Caroline B / Perreault, Mylene / Charbonneau, Mark R / Isabella, Vincent M / Hava, David L

Molecular systems biology

2022 Volume 18, Issue 3, Page(s) e10539

Abstract: Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered ... ...

Abstract	Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalate in the gut and lower urinary oxalate as a potential treatment for EH. Oral administration of SYNB8802 leads to significantly decreased urinary oxalate excretion in healthy mice and non-human primates, demonstrating the strain's ability to consume oxalate in vivo. A mathematical modeling framework was constructed that combines in vitro and in vivo preclinical data to predict the effects of SYNB8802 administration on urinary oxalate excretion in humans. Simulations of SYNB8802 administration predict a clinically meaningful lowering of urinary oxalate excretion in healthy volunteers and EH patients. Together, these findings suggest that SYNB8802 is a promising treatment for EH.
MeSH term(s)	Animals ; Computer Simulation ; Female ; Humans ; Hyperoxaluria/etiology ; Hyperoxaluria/urine ; Male ; Mice ; Oxalates/metabolism ; Oxalates/urine
Chemical Substances	Oxalates
Language	English
Publishing date	2022-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2193510-5
ISSN	1744-4292 ; 1744-4292
ISSN (online)	1744-4292
ISSN	1744-4292
DOI	10.15252/msb.202110539
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Article ; Online: An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria

David Lubkowicz / Nicholas G Horvath / Michael J James / Pasquale Cantarella / Lauren Renaud / Christopher G Bergeron / Ron B Shmueli / Cami Anderson / Jian‐Rong Gao / Caroline B Kurtz / Mylene Perreault / Mark R Charbonneau / Vincent M Isabella / David L Hava

Molecular Systems Biology, Vol 18, Iss 3, Pp n/a-n/a (2022)

2022

Abstract: Abstract Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an ... ...

Abstract	Abstract Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalate in the gut and lower urinary oxalate as a potential treatment for EH. Oral administration of SYNB8802 leads to significantly decreased urinary oxalate excretion in healthy mice and non‐human primates, demonstrating the strain's ability to consume oxalate in vivo. A mathematical modeling framework was constructed that combines in vitro and in vivo preclinical data to predict the effects of SYNB8802 administration on urinary oxalate excretion in humans. Simulations of SYNB8802 administration predict a clinically meaningful lowering of urinary oxalate excretion in healthy volunteers and EH patients. Together, these findings suggest that SYNB8802 is a promising treatment for EH.
Keywords	engineered bacteria ; enteric hyperoxaluria ; in silico modeling ; oxalate ; synthetic biology ; Biology (General) ; QH301-705.5 ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evaluation of polymeric gene delivery nanoparticles by nanoparticle tracking analysis and high-throughput flow cytometry.

Shmueli, Ron B / Bhise, Nupura S / Green, Jordan J

Journal of visualized experiments : JoVE

2013 , Issue 73, Page(s) e50176

Abstract: Non-viral gene delivery using polymeric nanoparticles has emerged as an attractive approach for gene therapy to treat genetic diseases(1) and as a technology for regenerative medicine(2). Unlike viruses, which have significant safety issues, polymeric ... ...

Abstract	Non-viral gene delivery using polymeric nanoparticles has emerged as an attractive approach for gene therapy to treat genetic diseases(1) and as a technology for regenerative medicine(2). Unlike viruses, which have significant safety issues, polymeric nanoparticles can be designed to be non-toxic, non-immunogenic, non-mutagenic, easier to synthesize, chemically versatile, capable of carrying larger nucleic acid cargo and biodegradable and/or environmentally responsive. Cationic polymers self-assemble with negatively charged DNA via electrostatic interaction to form complexes on the order of 100 nm that are commonly termed polymeric nanoparticles. Examples of biomaterials used to form nanoscale polycationic gene delivery nanoparticles include polylysine, polyphosphoesters, poly(amidoamines)s and polyethylenimine (PEI), which is a non-degradable off-the-shelf cationic polymer commonly used for nucleic acid delivery(1,3) . Poly(beta-amino ester)s (PBAEs) are a newer class of cationic polymers(4) that are hydrolytically degradable(5,6) and have been shown to be effective at gene delivery to hard-to-transfect cell types such as human retinal endothelial cells (HRECs)(7), mouse mammary epithelial cells(8), human brain cancer cells(9) and macrovascular (human umbilical vein, HUVECs) endothelial cells(10). A new protocol to characterize polymeric nanoparticles utilizing nanoparticle tracking analysis (NTA) is described. In this approach, both the particle size distribution and the distribution of the number of plasmids per particle are obtained(11). In addition, a high-throughput 96-well plate transfection assay for rapid screening of the transfection efficacy of polymeric nanoparticles is presented. In this protocol, poly(beta-amino ester)s (PBAEs) are used as model polymers and human retinal endothelial cells (HRECs) are used as model human cells. This protocol can be easily adapted to evaluate any polymeric nanoparticle and any cell type of interest in a multi-well plate format.
MeSH term(s)	Animals ; Endothelium, Vascular/physiology ; Flow Cytometry/instrumentation ; Flow Cytometry/methods ; Humans ; Mice ; Nanoparticles/analysis ; Nanoparticles/chemistry ; Polymers/analysis ; Polymers/chemistry ; Retinal Vessels/cytology ; Transfection/instrumentation ; Transfection/methods
Chemical Substances	Polymers ; poly(beta-amino ester)
Language	English
Publishing date	2013-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/50176
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Article ; Online: Anisotropic biodegradable lipid coated particles for spatially dynamic protein presentation.

Meyer, Randall A / Mathew, Mohit P / Ben-Akiva, Elana / Sunshine, Joel C / Shmueli, Ron B / Ren, Qiuyin / Yarema, Kevin J / Green, Jordan J

Acta biomaterialia

2018 Volume 72, Page(s) 228–238

Abstract: There has been growing interest in the use of particles coated with lipids for applications ranging from drug delivery, gene delivery, and diagnostic imaging to immunoengineering. To date, almost all particles with lipid coatings have been spherical ... ...

Abstract	There has been growing interest in the use of particles coated with lipids for applications ranging from drug delivery, gene delivery, and diagnostic imaging to immunoengineering. To date, almost all particles with lipid coatings have been spherical despite emerging evidence that non-spherical shapes can provide important advantages including reduced non-specific elimination and increased target-specific binding. We combine control of core particle geometry with control of particle surface functionality by developing anisotropic, biodegradable ellipsoidal particles with lipid coatings. We demonstrate that these lipid coated ellipsoidal particles maintain advantageous properties of lipid polymer hybrid particles, such as the ability for modular protein conjugation to the particle surface using versatile bioorthogonal ligation reactions. In addition, they exhibit biomimetic membrane fluidity and demonstrate lateral diffusive properties characteristic of natural membrane proteins. These ellipsoidal particles simultaneously provide benefits of non-spherical particles in terms of stability and resistance to non-specific phagocytosis by macrophages as well as enhanced targeted binding. These biomaterials provide a novel and flexible platform for numerous biomedical applications. Statement of significance: The research reported here documents the ability of non-spherical polymeric particles to be coated with lipids to form anisotropic biomimetic particles. In addition, we demonstrate that these lipid-coated biodegradable polymeric particles can be conjugated to a wide variety of biological molecules in a "click-like" fashion. This is of interest due to the multiple types of cellular mimicry enabled by this biomaterial based technology. These features include mimicry of the highly anisotropic shape exhibited by cells, surface presentation of membrane bound protein mimetics, and lateral diffusivity of membrane bound substrates comparable to that of a plasma membrane. This platform is demonstrated to facilitate targeted cell binding while being resistant to non-specific cellular uptake. Such a platform could allow for investigations into how physical parameters of a particle and its surface affect the interface between biomaterials and cells, as well as provide biomimetic technology platforms for drug delivery and cellular engineering.
MeSH term(s)	Animals ; Anisotropy ; Coated Materials, Biocompatible/chemistry ; Coated Materials, Biocompatible/pharmacokinetics ; Coated Materials, Biocompatible/pharmacology ; Lipids/chemistry ; Lipids/pharmacokinetics ; Lipids/pharmacology ; Macrophages/cytology ; Macrophages/metabolism ; Membranes, Artificial ; Mice ; Phagocytosis/drug effects ; Proteins/chemistry ; Proteins/pharmacokinetics ; Proteins/pharmacology ; RAW 264.7 Cells
Chemical Substances	Coated Materials, Biocompatible ; Lipids ; Membranes, Artificial ; Proteins
Language	English
Publishing date	2018-04-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2018.03.056
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Article ; Online: Injectable drug depot engineered to release multiple ophthalmic therapeutic agents with precise time profiles for postoperative treatment following ocular surgery.

Mohammadi, Maziar / Patel, Kisha / Alaie, Seyedeh P / Shmueli, Ron B / Besirli, Cagri G / Larson, Ronald G / Green, Jordan J

Acta biomaterialia

2018 Volume 73, Page(s) 90–102

Abstract: A multi-drug delivery platform is developed to address current shortcomings of post-operative ocular drug delivery. The sustained biodegradable drug release system is composed of biodegradable polymeric microparticles (MPs) incorporated into a bulk ... ...

Abstract	A multi-drug delivery platform is developed to address current shortcomings of post-operative ocular drug delivery. The sustained biodegradable drug release system is composed of biodegradable polymeric microparticles (MPs) incorporated into a bulk biodegradable hydrogel made from triblock copolymers with poly(ethylene glycol) (PEG) center blocks and hydrophobic biodegradable polyester blocks such as poly(lactide-co-glycolide) (PLGA), Poly(lactic acid) (PLA), or Poly(lactide-co-caprolactone) (PLCL) blocks. This system is engineered to flow as a liquid solution at room temperature for facile injection into the eye and then quickly gel as it warms to physiological body temperatures (approximately 37 °C). The hydrogel acts as an ocular depot that can release three different drug molecules at programmed rates and times to provide optimal release of each species. In this manuscript, the hydrogel is configured to release a broad-spectrum antibiotic, a potent corticosteroid, and an ocular hypotensive, three ophthalmic therapeutic agents that are essential for post-operative management after ocular surgery, each drug released at its own timescale. The delivery platform is designed to mimic current topical application of postoperative ocular formulations, releasing the antibiotic for up to a week, and the corticosteroid and the ocular hypotensive agents for at least a month. Hydrophobic blocks, such as PLCL, were utilized to prolong the release duration of the biomolecules. This system also enables customization by being able to vary the initial drug loading to linearly tune the drug dose released, while maintaining a constant drug release profile over time. This minimally invasive biodegradable multi-drug delivery system is capable of replacing a complex ocular treatment regimen with a simple injection. Such a depot system has the potential to increase patient medication compliance and reduce both the immediate and late term complications following ophthalmic surgery. Statement of significance: After ocular surgery, patients routinely receive multiple medications including antibiotics, steroids and ocular hypotensives to ensure optimal surgical outcomes. The current standard of care for postoperative treatment after ocular surgery involves using eye drops daily, which has limited effectiveness mainly due to poor patient adherence. To improve patient experience and outcomes, this article presents the first thermoresponsive hydrogel able to release multiple drug molecules for the application of post-operative treatment following ocular surgery. By varying the parameters such as hydrogel type and polymer hydrophobicity, the drug release profile, duration and dosage can finely be tuned. The approach presented in this article can readily be applied to other applications by simply changing the drug loaded in the drug delivery system.
MeSH term(s)	Adrenal Cortex Hormones/chemistry ; Adrenal Cortex Hormones/pharmacokinetics ; Adrenal Cortex Hormones/pharmacology ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacokinetics ; Anti-Bacterial Agents/pharmacology ; Drug Implants/chemistry ; Drug Implants/pharmacokinetics ; Drug Implants/pharmacology ; Humans ; Hydrogels/chemistry ; Hydrogels/pharmacokinetics ; Hydrogels/pharmacology ; Ophthalmologic Surgical Procedures ; Polyesters/chemistry ; Polyesters/pharmacokinetics ; Polyesters/pharmacology ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/pharmacokinetics ; Polyethylene Glycols/pharmacology ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer/pharmacokinetics ; Polylactic Acid-Polyglycolic Acid Copolymer/pharmacology ; Postoperative Care
Chemical Substances	Adrenal Cortex Hormones ; Anti-Bacterial Agents ; Drug Implants ; Hydrogels ; Polyesters ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS) ; polycaprolactone (24980-41-4) ; Polyethylene Glycols (3WJQ0SDW1A) ; poly(lactide) (459TN2L5F5)
Language	English
Publishing date	2018-04-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2018.04.037
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Article ; Online: Anisotropic poly(lactic-co-glycolic acid) microparticles enable sustained release of a peptide for long-term inhibition of ocular neovascularization.

Kim, Jayoung / Lima E Silva, Raquel / Shmueli, Ron B / Mirando, Adam C / Tzeng, Stephany Y / Pandey, Niranjan B / Ben-Akiva, Elana / Popel, Aleksander S / Campochiaro, Peter A / Green, Jordan J

Acta biomaterialia

2019 Volume 97, Page(s) 451–460

Abstract: Leading causes of vision loss include neovascular age-related macular degeneration (NVAMD) and macular edema (ME), which both require frequent intravitreal injections for treatment. A safe, poly(lactic-co-glycolic acid) (PLGA)-based biodegradable ... ...

Abstract	Leading causes of vision loss include neovascular age-related macular degeneration (NVAMD) and macular edema (ME), which both require frequent intravitreal injections for treatment. A safe, poly(lactic-co-glycolic acid) (PLGA)-based biodegradable polymeric microparticle (MP) delivery system was developed that encapsulates and protects a biomimetic peptide from degradation, allows sustained intraocular release through polymer hydrolysis, and demonstrates a prolonged anti-angiogenic effect in vivo in three different NVAMD animal models (a laser-induced choroidal neovascularization mouse model, a rhoVEGF transgenic mouse model, and a Tet/opsin/VEGF transgenic mouse model) following intravitreal administration. The role of copolymer composition and microparticle shape was explored and 85:15 lactide-to-glycolide PLGA formed into ellipsoidal microparticles was found to be effective at inhibiting neovascularization for at least 16 weeks in vivo. Treatments were found to not only inhibit the growth of neovascularization, but also to cause regression of the neovasculature, reduce vascular leakage, and prevent exudative retinal detachment. These particulate devices are promising for the sustained release of biologics in the eye and may be useful for treating retinal diseases. STATEMENT OF SIGNIFICANCE: Devastating retinal diseases cause blindness in millions of people around the world. Current protein-based treatments have insufficient efficacy for many patients and also necessitate frequent intravitreal injections. Here, we demonstrate a new treatment consisting of a peptide encapsulated in biodegradable microparticles. We explore the effects of copolymer composition and physical shape of polymeric microparticles and find that both modulate peptide release. Efficacy of the treatment was validated in three different mouse models and the lead formulation was determined to be effective long-term, for at least 16 weeks in vivo, following a single injection. Treatments inhibited and regressed neovascularization as well as reduced vascular leakage. Anisotropic polymeric microparticles are promising for the sustained release of biologics in the eye.
MeSH term(s)	Animals ; Anisotropy ; Biomimetic Materials/chemistry ; Biomimetic Materials/pharmacokinetics ; Biomimetic Materials/pharmacology ; Choroidal Neovascularization/genetics ; Choroidal Neovascularization/metabolism ; Choroidal Neovascularization/pathology ; Choroidal Neovascularization/prevention & control ; Delayed-Action Preparations/chemistry ; Delayed-Action Preparations/pharmacokinetics ; Delayed-Action Preparations/pharmacology ; Intravitreal Injections ; Mice ; Mice, Transgenic ; Peptides/chemistry ; Peptides/pharmacokinetics ; Peptides/pharmacology ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer/pharmacokinetics ; Polylactic Acid-Polyglycolic Acid Copolymer/pharmacology ; RAW 264.7 Cells
Chemical Substances	Delayed-Action Preparations ; Peptides ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS)
Language	English
Publishing date	2019-07-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2019.07.054
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Article ; Online: A novel assay for quantifying the number of plasmids encapsulated by polymer nanoparticles.

Bhise, Nupura S / Shmueli, Ron B / Gonzalez, Jose / Green, Jordan J

Small (Weinheim an der Bergstrasse, Germany)

2011 Volume 8, Issue 3, Page(s) 367–373

MeSH term(s)	Drug Compounding/methods ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Humans ; Light ; Nanoparticles/chemistry ; Nanoparticles/ultrastructure ; Nanotechnology/methods ; Particle Size ; Plasmids/metabolism ; Polyethyleneimine/chemistry ; Polymers/chemistry ; Scattering, Radiation ; Transfection
Chemical Substances	Polymers ; poly(beta-amino ester) ; Polyethyleneimine (9002-98-6)
Language	English
Publishing date	2011-12-05
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2168935-0
ISSN	1613-6829 ; 1613-6810
ISSN (online)	1613-6829
ISSN	1613-6810
DOI	10.1002/smll.201101718
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Article ; Online: Electrostatic surface modifications to improve gene delivery.

Shmueli, Ron B / Anderson, Daniel G / Green, Jordan J

Expert opinion on drug delivery

2010 Volume 7, Issue 4, Page(s) 535–550

Abstract: Importance of the field: Gene therapy has the potential to treat a wide variety of diseases, including genetic diseases and cancer.: Areas covered in this review: This review introduces biomaterials used for gene delivery and then focuses on the use ... ...

Abstract	Importance of the field: Gene therapy has the potential to treat a wide variety of diseases, including genetic diseases and cancer. Areas covered in this review: This review introduces biomaterials used for gene delivery and then focuses on the use of electrostatic surface modifications to improve gene delivery materials. These modifications have been used to stabilize therapeutics in vivo, add cell-specific targeting ligands, and promote controlled release. Coatings of nanoparticles and microparticles as well as non-particulate surface coatings are covered in this review. Electrostatic principles are crucial for the development of multilayer delivery structures fabricated by the layer-by-layer method. What the reader will gain: The reader will gain knowledge about the composition of biomaterials used for surface modifications and how these coatings and multilayers can be utilized to improve spatial control and efficiency of delivery. Examples are shown for the delivery of nucleic acids, including DNA and siRNA, to in vitro and in vivo systems. Take home message: The versatile and powerful approach of electrostatic coatings and multilayers will lead to the development of enhanced gene therapies.
MeSH term(s)	Biocompatible Materials ; Gene Transfer Techniques ; Nanoparticles ; Nucleic Acids/administration & dosage ; Static Electricity
Chemical Substances	Biocompatible Materials ; Nucleic Acids
Language	English
Publishing date	2010-07-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2167286-6
ISSN	1744-7593 ; 1742-5247
ISSN (online)	1744-7593
ISSN	1742-5247
DOI	10.1517/17425241003603653
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Article ; Online: Biomimetic peptide display from a polymeric nanoparticle surface for targeting and antitumor activity to human triple-negative breast cancer cells.

Bressler, Eric M / Kim, Jayoung / Shmueli, Ron B / Mirando, Adam C / Bazzazi, Hojjat / Lee, Esak / Popel, Aleksander S / Pandey, Niranjan B / Green, Jordan J

Journal of biomedical materials research. Part A

2018 Volume 106, Issue 6, Page(s) 1753–1764

Abstract: While poly(lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) can encapsulate drug cargos and prolong circulation times, they show nonspecific accumulation in off-target tissues. Targeted delivery of drugs to tumor tissue ... ...

Abstract	While poly(lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) can encapsulate drug cargos and prolong circulation times, they show nonspecific accumulation in off-target tissues. Targeted delivery of drugs to tumor tissue and tumor vasculature is a promising approach for treating solid tumors while enhancing specificity and reducing systemic toxicity. AXT050, a collagen-IV derived peptide with both antitumor and antiangiogenic properties, is shown to bind to tumor-associated integrins with high affinity, which leads to targeted accumulation in tumor tissue. AXT050 conjugated to PLGA-PEG NPs at precisely controlled surface density functions both as a targeting agent to human tumor cells and demonstrates potential for simultaneous antitumorigenic and antiangiogenic activity. These targeted NPs cause inhibition of adhesion and proliferation in vitro when added to human triple-negative breast cancer cells and microvascular endothelial cells through binding to integrin α
MeSH term(s)	Angiogenesis Inhibitors/administration & dosage ; Angiogenesis Inhibitors/pharmacokinetics ; Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacokinetics ; Cell Line, Tumor ; Drug Delivery Systems ; Female ; Humans ; Mice, Nude ; Nanoconjugates/chemistry ; Nanoparticles/chemistry ; Peptides/administration & dosage ; Peptides/pharmacokinetics ; Polyesters/chemistry ; Polyethylene Glycols/chemistry ; Tissue Distribution ; Triple Negative Breast Neoplasms/drug therapy
Chemical Substances	Angiogenesis Inhibitors ; Antineoplastic Agents ; Nanoconjugates ; Peptides ; Polyesters ; polyethylene glycol-poly(lactide-co-glycolide) ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2018-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.36360
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Article: Evaluation of polymeric gene delivery nanoparticles by nanoparticle tracking analysis and high-throughput flow cytometry

Shmueli, Ron B / Bhise, Nupura S / Green, Jordan J

Journal of visualized experiments. 2013 Mar. 01, , no. 73

2013

Abstract: Non-viral gene delivery using polymeric nanoparticles has emerged as an attractive approach for gene therapy to treat genetic diseases1 and as a technology for regenerative medicine2. Unlike viruses, which have significant safety issues, polymeric ... ...

Abstract	Non-viral gene delivery using polymeric nanoparticles has emerged as an attractive approach for gene therapy to treat genetic diseases1 and as a technology for regenerative medicine2. Unlike viruses, which have significant safety issues, polymeric nanoparticles can be designed to be non-toxic, non-immunogenic, non-mutagenic, easier to synthesize, chemically versatile, capable of carrying larger nucleic acid cargo and biodegradable and/or environmentally responsive. Cationic polymers self-assemble with negatively charged DNA via electrostatic interaction to form complexes on the order of 100 nm that are commonly termed polymeric nanoparticles. Examples of biomaterials used to form nanoscale polycationic gene delivery nanoparticles include polylysine, polyphosphoesters, poly(amidoamines)s and polyethylenimine (PEI), which is a non-degradable off-the-shelf cationic polymer commonly used for nucleic acid delivery1,3 . Poly(beta-amino ester)s (PBAEs) are a newer class of cationic polymers4 that are hydrolytically degradable5,6 and have been shown to be effective at gene delivery to hard-to-transfect cell types such as human retinal endothelial cells (HRECs)7, mouse mammary epithelial cells8, human brain cancer cells9 and macrovascular (human umbilical vein, HUVECs) endothelial cells10. A new protocol to characterize polymeric nanoparticles utilizing nanoparticle tracking analysis (NTA) is described. In this approach, both the particle size distribution and the distribution of the number of plasmids per particle are obtained11. In addition, a high-throughput 96-well plate transfection assay for rapid screening of the transfection efficacy of polymeric nanoparticles is presented. In this protocol, poly(beta-amino ester)s (PBAEs) are used as model polymers and human retinal endothelial cells (HRECs) are used as model human cells. This protocol can be easily adapted to evaluate any polymeric nanoparticle and any cell type of interest in a multi-well plate format.
Keywords	biocompatible materials ; biodegradability ; brain neoplasms ; electrostatic interactions ; endothelial cells ; epithelium ; flow cytometry ; gene therapy ; humans ; mice ; models ; nanoparticles ; particle size distribution ; plasmids ; polyethyleneimine ; rapid methods ; screening ; transfection ; umbilical veins ; viruses
Language	English
Dates of publication	2013-0301
Size	p. e50176.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/50176
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