Multi‐Step Assembly of an RNA‐Liposome Nanoparticle Formulation Revealed by Real‐Time, Single‐Particle Quantitative Imaging
Source abstract
Abstract
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.
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Research context
OpenAlex topics: RNA Interference and Gene Delivery · Advanced biosensing and bioanalysis techniques · Nanopore and Nanochannel Transport Studies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Division of Chemical Biology and Medicinal Chemistry College of Pharmacy University of Texas at Austin Austin TX 78712 USA
Department of Physics University of Florida Gainesville FL 32611 USA
Department of Neurosurgery Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, University of Florida Lillian S. Wells Gainesville FL 32610 USA
Department of Microbiology and Cell Science University of Florida Gainesville FL 32603 USA
Middlebury College Department of Physics McCardell Bicentennial Hall Middlebury VT 05753 USA
Department of Pediatrics Division of Pediatric Hematology Oncology University of Florida Gainesville FL 32610 USA
MD Anderson Cancer Center Division of Radiation Oncology University of Texas Houston TX 77030 USA
Funding
Florida Department of Health · National Institute of General Medical Sciences · National Cancer Institute · Food and Drug Administration
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