# Chitosan-functionalized mesoporous silica nanoparticles co-loaded with chrysin and quercetin: a potent strategy against lung cancer cells

**Authors:** Chou-Yi Hsu, Ammar Yasir Ahmed, Nahed S. Alharthi, Alanood S. Algarni, Fakhria A. Al Joufi, R. Roopashree, Zafar Aminov, Sumit Kaushal, Firas Sattar Gheni AL-Jabban, Khursheed Muzammil

PMC · DOI: 10.1038/s41598-025-29511-3 · Scientific Reports · 2026-01-05

## TL;DR

This study shows that chitosan-functionalized nanoparticles loaded with chrysin and quercetin effectively kill lung cancer cells by inducing apoptosis.

## Contribution

A novel nanoparticle formulation co-loading chrysin and quercetin is proposed for enhanced lung cancer treatment.

## Key findings

- The nanoparticles induced significant cell cycle arrest at the G0/G1 phase in A549 cells.
- Apoptosis-related genes like p53, Bax, and Fas were upregulated, while Bcl-2 and Cyclin D1 were downregulated.
- The IC₅₀ values of the nanoparticles were 1 µM and 2 µM after 24 and 48 hours, respectively.

## Abstract

Lung cancer (LC) represents a major and growing challenge in global healthcare, necessitating the exploration of innovative therapeutic strategies. In this context, nanoparticles (NPs) have emerged as promising platforms for enhancing treatment efficacy and improving patient outcomes. The present study investigated the cytotoxic effects of chitosan-functionalized mesoporous silica nanoparticles (MSNs) co-loaded with chrysin (Chr) and quercetin (Qur)—denoted as Chr–Qur@MSNs–Chi—on A549 lung cancer cells. Chr–Qur@MSNs–Chi NPs were synthesized and characterized using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Cell viability and apoptosis-related gene expression were evaluated using the MTT assay and quantitative real-time PCR (qRT-PCR), respectively.The synthesized NPs were spherical, with an average size range of 80–110 nm, and exhibited no detectable impurities. The DLS analysis indicated a particle size of approximately 110 nm and a zeta potential of − 36.5 mV. The MTT assay revealed IC₅₀ values of 1 µM and 2 µM after 24 and 48 h of treatment, respectively. Furthermore, Chr–Qur@MSNs–Chi induced greater cell cycle arrest at the G0/G1 phase compared to the free Chr–Qur combination. Gene expression analysis demonstrated significant upregulation of p53, Bax, and Fas (2.1-, 2.2-, and 2.4-fold, respectively), alongside downregulation of Cyclin D1, pRB, and Bcl-2 (0.6-, 0.8-, and 0.7-fold, respectively), indicating strong apoptotic effects (P < 0.001). These findings suggest that Chr–Qur@MSNs–Chi nanoparticles exhibit potent anticancer activity against A549 human lung cancer cells, likely through the induction of apoptosis and modulation of apoptosis-related gene expression pathways.

## Linked entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], FAS (Fas cell surface death receptor) [NCBI Gene 355], ccnd1.S (cyclin D1 S homeolog) [NCBI Gene 379161], RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596]
- **Chemicals:** chrysin (PubChem CID 5281607), quercetin (PubChem CID 5280343), chitosan (PubChem CID 129662530)
- **Diseases:** lung cancer (MONDO:0005138)

## Full-text entities

- **Diseases:** lung cancer (MESH:D008175)
- **Chemicals:** chrysin (MESH:C043561), quercetin (MESH:D011794), Chitosan (MESH:D048271), silica (MESH:D012822)

## Full text

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## Figures

14 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12775091/full.md

## References

6 references — full list in the complete paper: https://tomesphere.com/paper/PMC12775091/full.md

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Source: https://tomesphere.com/paper/PMC12775091