# Treatment of Maxillofacial Cancers by Zein Nanoparticles Loaded with Anticancer Peptide Pistacia Zardin1: Enhanced Cytotoxicity and Apoptosis Induction in Head and Neck Squamous Cell Carcinoma (HNSCC)

## TL;DR

Researchers developed zein nanoparticles loaded with an anticancer peptide to treat head and neck cancers, showing improved effectiveness and cancer cell targeting.

## Contribution

A novel pH-responsive nanoparticle delivery system for the anticancer peptide PZ1, enhancing its cytotoxicity and apoptosis in HNSCC.

## Key findings

- PZ1-Zein NPs reduced IC50 values in HNSCC cell lines compared to free peptide, showing higher efficacy.
- The nanoparticles increased caspase-3/7 activity, indicating enhanced apoptosis in cancer cells.
- PZ1-Zein NPs demonstrated improved selectivity for cancer cells over normal cells.

## Abstract

Head and neck squamous cell carcinomas (HNSCCs) are considered the most common histological type of head and neck cancer. This study aims to develop a drug delivery system based on zein protein nanoparticles (Zein NPs) to enhance the therapeutic effect of the anticancer peptide, Pistacia zardin1 (PZ1), for the treatment of maxillofacial cancers. PZ1-Zein NPs were synthesized by the desolvation method. These spherical nanoparticles (size: 162.8 nm, PDI: 0.27) showed high encapsulation efficiency (89%) and pH-responsive release (with higher drug release in the acidic tumor microenvironment). In vitro cytotoxicity assays showed that PZ1-Zein NPs significantly reduced IC50 values in HNSCC cell lines (e.g., SCC-25: 7.5 µM vs. 19.3 µM for free peptide, p < 0.001) while exhibiting improved selectivity for cancer cells over normal HaCaT cells. Mechanistic investigations confirmed that PZ1-Zein NPs significantly increased apoptosis, as shown by increased caspase-3/7 activity (5.8-fold vs. 2.6-fold). These findings highlight PZ1-Zein NPs as a promising nanomedicine strategy and a candidate functional component for future dual-functional scaffolds aimed at targeted hard tissue engineering and surgery in HNSCC management.