Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative Imaging
Abstract Self‐assembly plays a critical role in nanoparticle‐based applications. However, it remains challenging to monitor the self‐assembly of multi‐component nanomaterials at a single‐particle level, in real‐time, with high throughput, and in a model‐independent manner. Here, multi‐color fluoresc...
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| Format: | Article |
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202414305 |
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| author | Michael C. Chung Hector R. Mendez‐Gomez Dhruvkumar Soni Reagan McGinley Alen Zacharia Jewel Ashbrook Brian Stover Adam J. Grippin Elias J. Sayour Juan Guan |
| author_facet | Michael C. Chung Hector R. Mendez‐Gomez Dhruvkumar Soni Reagan McGinley Alen Zacharia Jewel Ashbrook Brian Stover Adam J. Grippin Elias J. Sayour Juan Guan |
| author_sort | Michael C. Chung |
| collection | DOAJ |
| description | Abstract Self‐assembly plays a critical role in nanoparticle‐based applications. However, it remains challenging to monitor the self‐assembly of multi‐component nanomaterials at a single‐particle level, in real‐time, with high throughput, and in a model‐independent manner. Here, multi‐color fluorescence microscopy is applied to track the assembly of both liposomes and mRNA simultaneously in clinical mRNA‐based cancer immunotherapy. Imaging reveals that the assembly occurs in discrete steps: initially, RNA adsorbs onto the liposomes; then, the RNA‐coated liposomes cluster into heterogeneous structures ranging from sub‐micrometer to tens of micrometers. The clustering process is consistent with a Smoluchowski model with a Brownian diffusion kernel. The transition between the two steps of assembly is determined by the orientation of RNA‐mediated interactions. Given the facile application of this approach and the ubiquity of the components studied, the imaging and analysis in this work are readily applied to monitor multi‐component assembly of diverse nanomaterials. |
| format | Article |
| id | doaj-art-d27a1920478d4a00843e38554dc36df8 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d27a1920478d4a00843e38554dc36df82025-08-20T02:49:46ZengWileyAdvanced Science2198-38442025-03-011212n/an/a10.1002/advs.202414305Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative ImagingMichael C. Chung0Hector R. Mendez‐Gomez1Dhruvkumar Soni2Reagan McGinley3Alen Zacharia4Jewel Ashbrook5Brian Stover6Adam J. Grippin7Elias J. Sayour8Juan Guan9Division of Chemical Biology and Medicinal Chemistry College of Pharmacy University of Texas at Austin Austin TX 78712 USADepartment of Neurosurgery Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, University of Florida Lillian S. Wells Gainesville FL 32610 USADepartment of Neurosurgery Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, University of Florida Lillian S. Wells Gainesville FL 32610 USADepartment of Microbiology and Cell Science University of Florida Gainesville FL 32603 USADepartment of Physics University of Florida Gainesville FL 32611 USAMiddlebury College Department of Physics McCardell Bicentennial Hall Middlebury VT 05753 USADepartment of Pediatrics Division of Pediatric Hematology Oncology University of Florida Gainesville FL 32610 USAMD Anderson Cancer Center Division of Radiation Oncology University of Texas Houston TX 77030 USADepartment of Neurosurgery Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, University of Florida Lillian S. Wells Gainesville FL 32610 USADivision of Chemical Biology and Medicinal Chemistry College of Pharmacy University of Texas at Austin Austin TX 78712 USAAbstract Self‐assembly plays a critical role in nanoparticle‐based applications. However, it remains challenging to monitor the self‐assembly of multi‐component nanomaterials at a single‐particle level, in real‐time, with high throughput, and in a model‐independent manner. Here, multi‐color fluorescence microscopy is applied to track the assembly of both liposomes and mRNA simultaneously in clinical mRNA‐based cancer immunotherapy. Imaging reveals that the assembly occurs in discrete steps: initially, RNA adsorbs onto the liposomes; then, the RNA‐coated liposomes cluster into heterogeneous structures ranging from sub‐micrometer to tens of micrometers. The clustering process is consistent with a Smoluchowski model with a Brownian diffusion kernel. The transition between the two steps of assembly is determined by the orientation of RNA‐mediated interactions. Given the facile application of this approach and the ubiquity of the components studied, the imaging and analysis in this work are readily applied to monitor multi‐component assembly of diverse nanomaterials.https://doi.org/10.1002/advs.202414305cancer‐therapydrug‐deliveryimagingnanomaterialsnanoparticlesquantitative imaging |
| spellingShingle | Michael C. Chung Hector R. Mendez‐Gomez Dhruvkumar Soni Reagan McGinley Alen Zacharia Jewel Ashbrook Brian Stover Adam J. Grippin Elias J. Sayour Juan Guan Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative Imaging Advanced Science cancer‐therapy drug‐delivery imaging nanomaterials nanoparticles quantitative imaging |
| title | Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative Imaging |
| title_full | Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative Imaging |
| title_fullStr | Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative Imaging |
| title_full_unstemmed | Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative Imaging |
| title_short | Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative Imaging |
| title_sort | multi step assembly of an rna liposome nanoparticle formulation revealed by real time single particle quantitative imaging |
| topic | cancer‐therapy drug‐delivery imaging nanomaterials nanoparticles quantitative imaging |
| url | https://doi.org/10.1002/advs.202414305 |
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