# Design and Synthesis of Peptide-Tagged Cubosome Nanocarriers for the Targeted Delivery of Paclitaxel in EGFR Overexpressing Breast Cancer

## TL;DR

Researchers created targeted nanocarriers to deliver paclitaxel to breast cancer cells overexpressing EGFR, reducing toxicity and improving treatment effectiveness.

## Contribution

This is the first demonstration of using peptide-functionalized cubosomes for active targeting of EGFR in cancer therapy.

## Key findings

- Peptide-tagged cubosomes showed 75% selective uptake in EGFR-overexpressing breast cancer cells.
- Paclitaxel-loaded cubosomes reduced MDA-MB-468 cell viability to 47% with minimal toxicity to HEK-293 cells.
- In vivo, targeted treatment suppressed tumor growth to 330 mm³ compared to 675 mm³ in untargeted groups.

## Abstract

Targeted delivery
of chemotherapeutic agents can reduce systemic
toxicity and enhance therapeutic outcomes by increasing the level
of drug accumulation at tumor sites. In this study, we developed lipid-based
cubosomal nanocarriers with an optimal size of 157 ± 20 nm for
effective tumor penetration. This work represents the first demonstration
of actively targeting cubosomes to epidermal growth factor receptors
(EGFR) using a short peptide ligand. The peptide-functionalized cubosomes
exhibited selective uptake of up to 75% in EGFR-overexpressing MDA-MB-468
breast cancer cells while showing minimal uptake (9%) in EGFR-negative
HEK-293 cells. Paclitaxel-loaded targeted cubosomes significantly
reduced MDA-MB-468 cell viability (47% survival at 60 μg/mL
after 24 h) with negligible cytotoxicity in HEK-293 cells (87% survival).
In 3D spheroid models, the survivability further decreased to 13%
in MDA-MB-468 spheroids after 48 h, whereas HEK-293 spheroids remained
largely unaffected. In vivo, targeted treatment suppressed
tumor progression, yielding a mean tumor volume of 330 mm3, compared to 675 mm3 and 770 mm3 in untargeted
and control groups, respectively, without observable liver or kidney
toxicity. These results highlight the therapeutic potential of peptide-tagged
cubosomes for the selective treatment of EGFR-expressing cancers.