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

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.