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Updated: May 9, 2026

Porous Silicon Microparticles for Delivery of siRNA Therapeutics

Porous Silicon Microparticles for Delivery of siRNA Therapeutics

Published on: January 15, 2015

Elucidating siRNA Cellular Delivery Mechanism Mediated by Quaternized Starch Nanoparticles.

Eliz Amar-Lewis^1,2, Limor Cohen³, Ramesh Chintakunta²

¹Ilse Katz Institute for Nanoscale Science & Technology, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.

Small (Weinheim an Der Bergstrasse, Germany)

|October 3, 2024

Summary

Quaternized starch nanoparticles efficiently deliver small interfering RNA (siRNA) into cells via endocytosis. However, endosomal escape and complex disassembly limit gene silencing, though ultrasound may enhance delivery.

Keywords:

delivery mechanism endocytosis particle tracking polysaccharide siRNA starch

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Area of Science:

Biomaterials Science
Nanotechnology
Drug Delivery Systems

Background:

Starch-based nanoparticles, including Quaternized starch (Q-starch), are promising for drug delivery due to their biocompatibility.
Q-starch facilitates the complexation of negatively charged small interfering RNA (siRNA) via quaternary amines.
Limited understanding of cellular mechanisms hinders the full efficacy of Q-starch/siRNA complexes for gene silencing.

Purpose of the Study:

To elucidate the cellular mechanism and kinetics of Quaternized starch/siRNA complexes.
To investigate the intracellular fate and endosomal escape of Q-starch/siRNA complexes.
To identify the rate-limiting steps in Q-starch/siRNA complex-mediated gene silencing.

Main Methods:

Single-particle tracking (SPT) to analyze intracellular complex dynamics.
Imaging flow cytometry for cell population-level analysis of cellular uptake and fate.
Experimental manipulations to assess endosomal escape and complex disassembly.

Main Results:

Q-starch/siRNA complexes are efficiently internalized by cells through endocytosis, with a significant portion trafficked to lysosomes.
Approximately 15% of internalized complexes achieve endosomal escape, offering potential for cytoplasmic gene silencing.
Complex disassembly was identified as the rate-limiting step, attributed to strong Q-starch/siRNA interactions.
Low-frequency ultrasound (20 kHz) application showed potential to induce siRNA release and accelerate gene silencing.

Conclusions:

Q-starch demonstrates efficient cellular uptake but faces challenges in endosomal escape and timely complex disassembly for optimal gene silencing.
The strong affinity between Q-starch and siRNA, while ensuring complex stability, impedes efficient release.
Ultrasound stimulation presents a potential strategy to overcome release limitations and enhance the kinetics of Q-starch/siRNA-mediated gene silencing.