Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming.

Monocytes / metabolism Nanoparticles / chemistry RNA, Messenger / genetics Animals Mice Humans Polyelectrolytes / chemistry Macrophages / metabolism Polyamines / chemistry Particle Size Cell Differentiation Gene Transfer Techniques Dendritic Cells / metabolism Static Electricity Polymers
mRNA delivery monocyte transfection nanoparticle assembly poly(beta-amino ester) vehicle size-mediated passive targeting

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
27 Aug 2024
Historique:
medline: 22 8 2024
pubmed: 22 8 2024
entrez: 22 8 2024
Statut: ppublish

Résumé

Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces. Specifically, our strategy permits controlled assembly of small poly(β-amino ester)/messenger ribonucleic acid (mRNA) nanoparticles into particles with a size that is kinetically tunable between 200 and 1,000 nm with high colloidal stability in physiological media. We found that assembled particles with an average size of 400 nm safely and most efficiently transfect monocytes following intravenous administration and mediate their differentiation into macrophages in the periphery. When a CpG adjuvant is co-loaded into the particles with an antigen mRNA, the monocytes differentiate into inflammatory dendritic cells and prime adaptive anticancer immunity in the tumor-draining lymph node. This platform technology offers a unique ligand-independent, particle-size-mediated strategy for preferential mRNA delivery and enables therapeutic paradigms

Identifiants

DOI: 10.1073/pnas.2400194121 PMID: 39172792
pubmed: 39172792
doi: 10.1073/pnas.2400194121
doi:

Substances chimiques

RNA, Messenger 0
Polyelectrolytes 0
polycations 0
Polyamines 0
poly(beta-amino ester) 0
Polymers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2400194121

Subventions

Organisme : HHS | NIH | National Cancer Institute (NCI)
ID : R01CA281143
Organisme : HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : U01AI155313
Organisme : HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : R21AI160738
Organisme : HHS | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)
ID : P41EB028239
Organisme : HHS | NIH | National Cancer Institute (NCI)
ID : R37CA246699

Déclaration de conflit d'intérêts

Competing interests statement:S.K.R., J.J.G. and H.-Q.M. are cofounders of Wyverna Therapeutics Inc. Y.H. was a consultant for Wyverna Therapeutics Inc. Y.H., S.Y.T., L.C., J.J.G. and H.-Q.M. are inventors of a patent application covering the nanoparticle assembly technology described here; S.Y.T., D.R.W., Y.R. and J.J.G. are inventors of a patent application covering the PBAE structures described here.Both patents were filed through and are managed by Johns Hopkins Technology Ventures. The other authors declare no conflict of interest.

Auteurs

Yizong Hu (Y)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
ORCID: 0000-0003-3983-5104

Stephany Y Tzeng (SY)

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
ORCID: 0000-0002-7561-482X

Leonardo Cheng (L)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Jinghan Lin (J)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.

Andres Villabona-Rueda (A)

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
ORCID: 0000-0002-6529-7162

Shuai Yu (S)

Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208.
ORCID: 0009-0001-9664-3937

Sixuan Li (S)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218.
ORCID: 0000-0002-0116-8812

Zachary Schneiderman (Z)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.

Yining Zhu (Y)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Jingyao Ma (J)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.

David R Wilson (DR)

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Sydney R Shannon (SR)

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
ORCID: 0000-0003-0474-0869

Tiarra Warren (T)

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
ORCID: 0000-0003-2061-490X

Yuan Rui (Y)

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Chenhu Qiu (C)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.

Erin W Kavanagh (EW)

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
ORCID: 0000-0002-8206-3923

Kathryn M Luly (KM)

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Yicheng Zhang (Y)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.

Nicole Korinetz (N)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.
ORCID: 0000-0001-7723-8883

Franco R D'Alessio (FR)

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Tza-Huei Wang (TH)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218.
ORCID: 0000-0002-3540-9354

Efrosini Kokkoli (E)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.
ORCID: 0000-0001-7783-0158

Sashank K Reddy (SK)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287.

Erik Luijten (E)

Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208.
Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, IL 60208.
Department of Chemistry, Northwestern University, Evanston, IL 60208.
Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208.
ORCID: 0000-0003-2364-1866

Jordan J Green (JJ)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.
ORCID: 0000-0003-4176-3808

Hai-Quan Mao (HQ)

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.
ORCID: 0000-0002-4262-9988

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Monocytes › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Eucaryotes › Animaux › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Structures macromoléculaires › Polyélectrolytes › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Composés chimiques organiques › Amines › Polyamines › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Phénomènes chimiques › Taille de particule › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Techniques de transfert de gènes › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système phagocytaire mononucléé › Cellules dendritiques › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Phénomènes physiques › Phénomènes magnétiques › Phénomènes électromagnétiques › Électricité › Électricité statique › Supramolecular assembly of polycation/mRNA...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Supramolecular assembly of polycation/mRNA...