High transfection ef ficiency of quantum dotantisense oligonucleotide nanoparticles in cancer cells through dual-receptor synergistic targeting

摘要

Incorporating ligands with nanoparticle-based carriers for specific delivery of therapeutic nucleic acids (such as antisense oligonucleotides and siRNA) to tumor sites is a promising approach in anti-cancer strategies. However, nanoparticle-based carriers remain insufficient in terms of the selectivity and transfection ef ficiency. In this paper, we designed a dual receptor-targeted QDs gene carrier QD-(AS-ODN+GE11+c(RGDfK)) which could increase the cellular uptake ef ficiency and further enhance the transfection ef ficiency. Here, the targeting ligands used were peptides GE11 and c(RGDfK) which could recognize epidermal growth factor receptors (EGFR) and integrin ανβ 3 receptors, respectively. Quantitative flow cytometry and ICP/MS showed that the synergistic effect between EGFR and integrin ανβ 3 increased the cellular uptake of QDs carriers. The effects of inhibition agents showed the endocytosis pathway of QD-(AS-ODN +GE11+c(RGDfK)) probe was mainly clathrin-mediated. Western blot confirmed that QD-(AS-ODN+GE11+c(RGDfK)) could further enhance gene silencing ef ficiency compared to QD-(AS-ODN+GE11) and QD-(AS-ODN+c(RGDfK)), suggesting this dual receptor-targeted gene carrier achieved desired transfection ef ficiency. In this gene delivery system, QDs could not only be used as a gene vehicle but also as fluorescence probe, allowing for localization and tracking during the delivery process. This transport model is very well referenced for non-viral gene carriers to enhance the targeting ability and transfection ef ficiency.