Caveolar Endocytosis Governs Nanoneedle Transfection.

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 del

SUBMITTER: Sun N 

PROVIDER: S-EPMC12918721 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature