Synthesis Folate-linked Chitosan-coated Quetiapine/BSA Nano-Carriers as the Efficient Targeted Anti-Cancer Drug Delivery System

Hussein Nadhim Ghafil Al-Hasnawi; Vahid Pouresmaeil; Fatemeh Davoodi-Dehaghani; Sara Rahban; Aida Pouresmaeil; Masoud Homayouni Tabrizi

doi:10.1007/s12033-023-00858-0

Synthesis Folate-linked Chitosan-coated Quetiapine/BSA Nano-Carriers as the Efficient Targeted Anti-Cancer Drug Delivery System

Mol Biotechnol. 2023 Aug 26. doi: 10.1007/s12033-023-00858-0. Online ahead of print.

Authors

Hussein Nadhim Ghafil Al-Hasnawi¹, Vahid Pouresmaeil², Fatemeh Davoodi-Dehaghani³, Sara Rahban⁴, Aida Pouresmaeil⁴, Masoud Homayouni Tabrizi⁴

Affiliations

¹ Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
² Department of Biochemistry, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran. vahidpouresmail@yahoo.fr.
³ Department of Biology, Faculty of Basic Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
⁴ Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

PMID: 37633875
DOI: 10.1007/s12033-023-00858-0

Abstract

Quetiapine (QTP) has been known to suppress cancer progression in patients suffering from mental disorders. This study aimed to produce the folate-linked chitosan-coated quetiapine/BSA nano-carriers (FCQB-NCs) and evaluate their antioxidant, apoptotic, and anti-metastatic potentials on prostate, pancreas, colon, and breast cancer cell lines. The FCQB-NCs were designed, produced, and characterized using DLS, FESEM, FTIR, and Zeta potential techniques. The nano-carriers antioxidant activity was studied by applying ABTS, DPPH, and FRAP assays. The FCQB-NCs' cytotoxicity and apoptotic/metastatic properties were evaluated utilizing MTT assay and qPCR-based analysis for measuring the apoptotic (Nf-KB)/metastatic (MMP2, MMP9, and MMP13) gene expression, respectively. The AO/PI fluorescent cell staining, DAPI staining, and scratch assay methods were conducted to verify the apoptotic and anti-metastatic activities of FCQB-NCs. The 51-nm FCQB-NCs (PDI = 0.26) exhibited antioxidant activity and selectively decreased the MDA-MB-231 cancer cells' viability by inducing Nf-KB overexpression, which caused the apoptosis pathway activation. Moreover, the FCQB-NCs suppressed the MDA-MB-231 cells' metastatic activity by down-regulating the MMP2, MMP9, and MMP13 gene expression, verified by detecting the decreased migration rate. The FCQB-NCs selectively induced apoptosis and suppressed metastasis in the human breast cancer cell line, which can be attributed to the stepwise release of QTP in two primary (extra-cellular release) and secondary (intra-cellular release) phases. The efficient selective cytotoxic impact of FCQB-NCs can be due to the novel stepwise release mechanism of the FCQB-NCs based on the two-phase entrapment of QTP by BSA and chitosan molecules. Therefore, FCQB-NCs have the potential to be used as an efficient selective anti-breast cancer.

Keywords: Anti-metastatic activity; Apoptotic activity; Cancer-selective cytotoxicity; Folate-linked chitosan-coated quetiapine/BSA nano-carriers (FCQB-NCs).