Caveolar Endocytosis Governs Nanoneedle Transfection
Source abstract
Abstract
Nanoneedles are emerging as a safe and scalable strategy for the genetic modification of primary human cells. However, a limited understanding of how interactions at the biointerface lead to functional gene expression continues to hinder clinical translation. While direct membrane penetration, permeabilization, and endocytosis have been proposed as intracellular delivery avenues, the mechanistic connection between delivery and successful transfection remains unclear. Here, we identify caveolae-mediated endocytosis, dependent on Caveolin-1, as a key mechanism enabling nanoneedle transfection. By selectively modulating Caveolin-1 expression in primary human regulatory T cells and MG63 cells and investigating endolysosomal processing, we show that although nucleic acids can be efficiently delivered in the absence of Caveolin-1, gene expression occurs only when caveolar endocytosis is present. These findings reveal a mechanistic basis and establish a broader design principle for nanoneedle transfection: interfacing must be accompanied by the engagement of permissive cellular trafficking pathways to achieve gene expression.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Caveolin-1 and cellular processes · RNA Interference and Gene Delivery · Extracellular vesicles in disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Centre for Craniofacial and Regenerative Biology
King’s College London
Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine
London Centre for Nanotechnology
Wenzhou Eye Valley Innovation Centre, Eye Hospital
Wenzhou Medical University
St John’s Institute of Dermatology, School of Basic & Medical Biosciences
State Key Laboratory of Oral Diseases & National Centre for Stomatology & National Clinical Research Centre for Oral Diseases, West China Hospital of Stomatology
Sichuan University
Department of Prosthodontics, West China Hospital of Stomatology
Centre for Gene Therapy & Regenerative Medicine
Department of Physics and Astronomy
University of Turku
Department of Life Sciences, Centre for Inflammation Research and Translational Medicine
Brunel University London
Funding
King's College London · Medical Research Council · European Research Council · China Scholarship Council
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