Proton-Sponge Coated Quantum Dots for siRNA Delivery and Intracellular Imaging

TLDR

The study designs multifunctional quantum‑dot nanoparticles coated with proton‑sponges for siRNA delivery and imaging. These nanoparticles combine balanced tertiary amine/carboxyl groups to overcome delivery barriers and serve as dual‑modality optical and electron‑microscopy probes for real‑time tracking. They achieve 10–20‑fold higher gene silencing and 5–6‑fold lower toxicity than existing transfection agents in MDA‑MB‑231 cells, advancing nanoparticle imaging and therapy.

Abstract

We report the rational design of multifunctional nanoparticles for short-interfering RNA (siRNA) delivery and imaging based on the use of semiconductor quantum dots (QDs) and proton-absorbing polymeric coatings (proton sponges). With a balanced composition of tertiary amine and carboxylic acid groups, these nanoparticles are specifically designed to address longstanding barriers in siRNA delivery such as cellular penetration, endosomal release, carrier unpacking, and intracellular transport. The results demonstrate dramatic improvement in gene silencing efficiency by 10−20-fold and simultaneous reduction in cellular toxicity by 5−6-fold, when compared directly with existing transfection agents for MDA-MB-231 cells. The QD−siRNA nanoparticles are also dual-modality optical and electron-microscopy probes, allowing real-time tracking and ultrastructural localization of QDs during delivery and transfection. These new insights and capabilities represent a major step toward nanoparticle engineering for imaging and therapeutic applications.