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A Modular Encapsulation System for Precision Delivery of Proteins, Nucleic Acids, and Small Molecules.

Thai D Luong¹, Nick Martel¹, James Rae¹

¹Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.

|December 12, 2025

Summary

Researchers developed caveospheres, a novel nanovesicle delivery system, for precise therapeutic delivery. This system efficiently targets cells, offering improved gene delivery and effective in vivo tumor treatment.

Keywords:

breast cancer targeting and treatment caveosphere (lipid nanoparticles)endosomal escape targeted delivery of DNA and mRNA virus-like particles of SARS-CoV-2

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Area of Science:

Biotechnology
Nanomedicine
Molecular Biology

Background:

Targeted nanoparticles offer revolutionary therapeutic potential.
Efficient and specific delivery of therapeutic payloads to target cells remains a challenge.

Purpose of the Study:

To demonstrate the utility of a flexible nanovesicle delivery system, termed caveospheres, for functional delivery of various biomolecules and drugs.
To evaluate the efficacy and specificity of caveospheres for targeted gene delivery and in vivo tumor treatment.

Main Methods:

Caveospheres were generated using the protein caveolin and loaded with RNA, DNA, proteins, or drugs.
Functionalized caveospheres were characterized for stability, cellular uptake, and cargo delivery efficiency.
The system's performance was compared to lipid-mediated gene delivery.
Caveospheres were engineered to display SARS-CoV-2-RBD for targeted delivery to human bronchial epithelial cells.
In vivo studies were conducted to assess tumor-killing efficacy.

Main Results:

Caveospheres demonstrated high stability in biological fluids and specific uptake by target-positive cells.
Efficient delivery of proteins, DNA, and mRNA to the cytoplasm and nuclei of target cells was achieved.
Negligible off-target transduction and uniform targeted expression were observed, outperforming lipid-mediated delivery.
Engineered caveospheres successfully targeted human bronchial epithelial cells.
Significant efficacy in precision tumor killing in vivo was demonstrated.

Conclusions:

Caveospheres represent a versatile and effective nanovesicle system for targeted delivery of diverse therapeutic payloads.
This system offers significant advantages over existing methods for gene delivery and demonstrates potential for in vivo cancer therapy.