# LinTT1-Functionalized Hybrid Lipid–Polymer Nanoparticles for Glioblastoma Targeting

**Authors:** Antonella Rocchi, Valeria Sidorenko, Nicola d’Avanzo, Luca Marchetti, Jhalak Sethi, Luigi Ciriolo, Anna Maria Tolomeo, Maria Grazia Cifone, Paola Palumbo, Massimo Fresta, Tambet Teesalu, Christian Celia

PMC · DOI: 10.1021/acsptsci.5c00537 · 2025-09-30

## TL;DR

Researchers developed a new nanoparticle system that targets glioblastoma brain tumors more effectively, improving drug delivery and treatment outcomes.

## Contribution

A novel hybrid lipid-polymer nanoparticle functionalized with LinTT1 peptide for targeted glioblastoma drug delivery is introduced.

## Key findings

- LinTT1-HLPNs bind selectively to glioblastoma cells in vitro and enhance the cytotoxicity of temozolomide.
- In vivo, LinTT1-HLPNs improve TMZ accumulation in tumor areas in murine glioblastoma models.
- The nanoplatform combines lipid-polymer benefits with a targeting strategy to address glioblastoma challenges.

## Abstract

Glioblastoma multiforme (GBM) is an aggressive brain
tumor with
limited therapeutic options and a poor prognosis. We developed hybrid
lipid-polymer nanoparticles (HLPNs) functionalized with tumor-homing
C-end Rule peptide LinTT1 (LinTT1-HLPNs) to improve the GBM targeting. In vitro studies demonstrated that LinTT1-HLPNs bind selectively
to GBM cells and significantly improved the cytotoxicity of the loaded
temozolomide (TMZ) (LinTT1-HLPNs@TMZ) compared to that of the free
drug. In vivo, intravenous injection of HLPNs in
both infiltrative and noninfiltrative GBM murine models had an enhanced
accumulation of TMZ in the tumor area, thus endorsing the selective
targeting and tissue penetration of LinTT1-HLPNs. This nanoplatform
combines the advantages of hybrid lipid–polymer nanoparticles
with a GBM-specific targeting strategy, thus providing an improved
drug delivery and therapeutic effect by a multistep targeting approach,
which addresses the key challenge of GBM.

## Linked entities

- **Chemicals:** temozolomide (PubChem CID 5394), TMZ (PubChem CID 5394)
- **Diseases:** Glioblastoma multiforme (MONDO:0018177), glioblastoma (MONDO:0018177)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** cytotoxicity (MESH:D064420), tumor (MESH:D009369), GBM (MESH:D005909), brain tumor (MESH:D001932)
- **Chemicals:** Lipid (MESH:D008055), TMZ (MESH:D000077204), Polymer (MESH:D011108), LinTT1 (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12519261/full.md

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Source: https://tomesphere.com/paper/PMC12519261