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Preparation and Characterization of Nanoliposomes for the Entrapment of Bioactive Hydrophilic Globular Proteins

Preparation and Characterization of Nanoliposomes for the Entrapment of Bioactive Hydrophilic Globular Proteins

Published on: August 31, 2019

Biofluid specific protein coronas affect lipid nanoparticle behavior in vitro.

Demian van Straten¹, Helena Sork², Luuk van de Schepop¹

¹CDL Research, University Medical Center Utrecht, Utrecht, the Netherlands.

Journal of Controlled Release : Official Journal of the Controlled Release Society

|July 20, 2024

Summary

Lipid nanoparticles (LNPs) develop different protein coronas in cerebrospinal fluid (CSF) versus plasma. This alters cellular uptake, highlighting the importance of administration site for LNP gene therapy efficacy.

Keywords:

Biofluids Brain Characterization Lipid nanoparticles Protein corona RNA delivery

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Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications

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Published on: November 17, 2015

Area of Science:

Biomedical Engineering
Nanotechnology
Drug Delivery

Background:

Lipid nanoparticles (LNPs) are established for mRNA/siRNA therapeutics, including COVID-19 vaccines.
Understanding in vivo LNP behavior, especially cell targeting via protein coronas, remains limited.
Tissue-specific protein coronas arise from different administration sites, impacting LNP properties.

Purpose of the Study:

To investigate differences in protein coronas formed on LNPs in human cerebrospinal fluid (CSF) versus plasma.
To assess the impact of CSF-derived protein coronas on LNP cellular uptake.
To evaluate if altered cellular uptake translates to improved cargo delivery.

Main Methods:

Incubation of a clinically relevant LNP formulation in human plasma and human CSF.
Proteomic analysis of the resulting protein coronas (plasma-derived vs. CSF-derived).
In vitro assessment of cellular uptake of LNPs with different protein coronas.

Main Results:

LNPs incubated in CSF (C-LNPs) exhibited a distinct protein corona composition compared to those in plasma (P-LNPs).
Apolipoprotein E and lipoproteins were more abundant in the C-LNP corona.
C-LNPs showed enhanced cellular uptake compared to P-LNPs, irrespective of cell type.

Conclusions:

Biofluid-specific protein coronas significantly alter LNP functionality.
The site of LNP administration can influence therapeutic efficacy due to differential corona formation.
Further research is needed to correlate enhanced cellular uptake with actual cargo delivery efficiency.