Journal of controlled release : official journal of the Controlled Release SocietyJan 6, 2026

Lipid nanoparticles targeting CD44 to improve CRISPR-Cas9 delivery for cancer gene editing

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

CD44-specific peptide-modified lipid nanoparticles achieved significant inhibition of tumor growth in melanoma models.

Gene editing technologies like CRISPR/Cas9 could target cancer-specific genes but face delivery challenges.
Lipid nanoparticles are effective at protecting and transporting gene editing tools.
The developed nanoparticles specifically delivered CRISPR/Cas9 mRNA and guide RNA to melanoma cells.
Inhibition of tumor growth was observed in both in vitro and in vivo models of skin melanoma.
The platform demonstrated the ability to reach metastatic melanoma in the brain, leading to reduced tumor growth.

Simplified

Skin cancer is the third most common malignancy, with melanoma being the most challenging due to its resistance to current therapies. Gene editing technologies like CRISPR/Cas9 offer a promising strategy for targeting cancer-specific genes, but the efficient delivery of these tools to tumor sites remains a significant challenge. Lipid nanoparticles (LNPs) have emerged as the leading platform for gene editing tools due to their ability to protect and transport large payloads. To enhance the precision of gene editing in melanoma, we developed CD44-specific peptide-modified LNPs for targeted delivery of CRISPR/Cas9 mRNA and guide RNA against polo-like kinase 1 (sgPLK1). Our approach led to enhanced targeting and gene editing efficacy by specifically delivering CRISPR/Cas9 and sgPLK1 to melanoma tumor cells, resulting in significant inhibition of tumor growth in both in vitro and in vivo skin melanoma models. Moreover, this platform showed the capacity to reach metastatic melanoma in the brain and resulting in substantial suppression of tumor growth in brain metastasis models. We envision that this peptide-modification strategy could be further employed to improve the targeting capabilities and therapeutic outcomes of LNPs for CRISPR/Cas9-based gene editing, paving the way for more precise and effective cancer treatments.

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Lipid nanoparticles targeting CD44 to improve CRISPR-Cas9 delivery for cancer gene editing

Abstract

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