Affiliations 

  • 1 Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), IMU University, Kuala Lumpur, 57000, Malaysia
  • 2 Centre for Stem Cell Research, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Shah Alam, 43000, Selangor, Malaysia
  • 3 Nanotechnology Research Group, Center for Nanotechnology and Advanced Materials, University of Nottingham Malaysia, Semenyih, 43500, Selangor, Malaysia. [email protected]
  • 4 Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), IMU University, Kuala Lumpur, 57000, Malaysia. [email protected]
Sci Rep, 2024 Dec 03;14(1):30098.
PMID: 39627280 DOI: 10.1038/s41598-024-80646-1

Abstract

Small interfering RNAs (siRNA) technology has emerged as a promising therapeutic tool for human health conditions like cancer due to its ability to regulate gene silencing. Despite FDA-approved, their delivery remains localized and limiting their systemic use. This study used single-walled carbon nanotubes (SWNTs) functionalized with polyethylene glycolated (PEGylated) phospholipids (PL-PEG) derivatives for systemic siRNA delivery. We developed an siRNA systemic delivery vehicle (SWNT-siRNA) by conjugating SWNT functionalized with PL-PEG containing either amine (PA) or maleimide (MA). The functionalized SWNT with a lower molecular weight of PA produced the SWNT-siRNA conjugate system with the highest stability and high siRNA loading quantity. The system delivered siRNA to a panel of tumour cell lines of different organs (i.e. HeLa, H1299 and MCF-7) and a non-cancerous human embryonic kidney 293 cells (HEK293T) with high biocompatibility and low toxicity. The cellular uptake of SWNT-siRNA conjugates by epithelial cells was found to be energy dependent. Importantly, the presence of P-glycoprotein, a marker for drug resistance, did not inhibit SWNT-mediated siRNA delivery. Mouse xenograft model further confirmed the potential of SWNT-siRNA conjugates with a significant gene knock-down without signs of acute toxicity. These findings pave the way for potential gene therapy applications using SWNTs as delivery vehicles.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.