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Related Experiment Video

Updated: Jan 23, 2026

Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery

Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery

Published on: April 16, 2019

Membrane fusogenic high-density lipoprotein nanoparticles.

Hyungjin Kim¹, Tomohiro Nobeyama², Shinnosuke Honda³

¹Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University Institute for Advanced Study (KUIAS), Sakyo-ku, Kyoto 606-8501, Japan.

Biochimica Et Biophysica Acta. Biomembranes

|June 18, 2019

Summary

Researchers developed HDL nanoparticles with virus-like fusion activity for drug delivery. One mutant showed enhanced lipid mixing and cell membrane binding, offering a novel strategy for drug carriers.

Keywords:

Cell-penetrating peptide Lipid mixing Lipoproteins Mildly acidic pH

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Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery

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High-Density Lipoprotein-Specific Phospholipid Efflux Assay

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Published on: September 30, 2025

Area of Science:

Biotechnology
Nanomedicine
Cell Biology

Background:

Membrane fusion at acidic pH is crucial for viral entry and nanoparticle drug delivery.
Endosomal entrapment limits the efficacy of conventional nanoparticle drug carriers.
High-density lipoprotein (HDL) nanoparticles offer a potential platform for drug delivery.

Purpose of the Study:

To engineer HDL nanoparticles with virus-like membrane fusion capabilities.
To investigate the pH-dependent fusogenic activity of modified HDL nanoparticles.
To evaluate HDL-based nanoparticles as potential drug carriers for enhanced cellular uptake.

Main Methods:

Constructed HDL mutants by incorporating cell-penetrating peptides (TAT, penetratin, Arg8) into the HDL structure.
Performed lipid-mixing assays with anionic liposomes at pH 5.5 to assess fusogenic activity.
Evaluated HDL mutant binding and fusion activity with live mammalian cells under varying pH and serum conditions.

Main Results:

One engineered HDL mutant exhibited fusogenic activity exceeding that of known fusogenic liposomes at pH 5.5.
This HDL mutant demonstrated significant plasma membrane binding in mammalian cells, independent of pH in the presence of serum.
In serum-free conditions, the HDL mutant showed pH-dependent plasma membrane binding and subsequent lipid mixing.

Conclusions:

Engineered HDL nanoparticles can be endowed with virus-like fusogenic properties.
Modified HDL nanoparticles represent a promising strategy for overcoming endosomal entrapment in drug delivery.
The HDL lipid/protein composite structure can be leveraged for developing advanced drug carriers.