# Delivery of Antisense Oligonucleotides Using the Nano‐Cell Vesicle Technology System (nCVTs) for Targeted Cancer Therapy

**Authors:** Yi Hsuan Ou, Wei Heng Chng, Ram Pravin Kumar Muthuramalingam, Prathyusha Raghunathan, Nichakan Khunkitchai, Choon Keong Lee, Jae Ha Jun, Zi Xiu Ng, Phua Tian Xin, Wei Jiang Goh, Jiong‐Wei Wang, Bertrand Czarny

PMC · DOI: 10.1002/smll.202509094 · Small (Weinheim an Der Bergstrasse, Germany) · 2025-12-16

## TL;DR

Researchers developed a new delivery system for cancer therapies using nano-cell vesicles, which efficiently transport antisense drugs into cancer cells and reduce tumor growth.

## Contribution

The study introduces nano-cell vesicle technology (nCVTs) as a novel delivery system for nucleic acid therapeutics with enhanced targeting and reduced toxicity.

## Key findings

- nCVTs outperformed liposomes and free AS014 in delivering antisense oligonucleotides into cancer cells.
- nCVTs achieved efficient delivery to both cytoplasm and nuclei with lower cytotoxicity.
- nCVTsAS014 significantly inhibited tumor growth in vivo, showing strong therapeutic potential.

## Abstract

Nucleic acid therapeutics (NATs) promise to revolutionize the fight against diseases like cancer, yet their full potential remains untapped due to significant delivery challenges. In this study, innovative nano‐cell vesicle technology systems (nCVTs) are developed to target NATs to cancer cells. nCVTs are created by fusing cationic lipids with pre‐emptied cell membranes that can efficiently bind and transport NATs such as antisense oligonucleotides (ASOs). In the study, nCVTs loaded with an anti‐cancer ASO, AS014 (nCVTsAS014) outperformed both liposomes and free AS014 in delivering the therapeutic payload into cancer cells, reaching both the cytoplasm and nuclei with remarkable efficiency while displaying lower intrinsic cytotoxicity. Most impressively, nCVTsAS014 demonstrated potent inhibition of tumor growth in vivo, underscoring its potential as a powerful cancer therapy platform. Altogether, the findings highlight nCVTs as a promising strategy to unlock the therapeutic power of NATs, paving the way toward more effective and targeted treatments for cancer.

Nano‐Cell Vesicle Technology (nCVTs) integrates cationic lipids with tumor‐homing cell membranes to achieve efficient intracellular transport of antisense oligonucleotides. The system enhances nuclear delivery, minimizes cytotoxicity, and suppresses tumor growth in vivo, establishing nCVTs as a versatile and biocompatible platform for next‐generation nucleic acid cancer therapeutics.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Diseases:** Cancer (MESH:D009369), cytotoxicity (MESH:D064420)
- **Chemicals:** AS014 (-), lipids (MESH:D008055), ASOs (MESH:D016376)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12877987/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12877987/full.md

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Source: https://tomesphere.com/paper/PMC12877987