合成叶酸连接的壳聚糖包被奎替必新/Bovine Serum Albumin纳米载体作为高效靶向抗癌药物输送系统。
Synthesis Folate-linked Chitosan-coated Quetiapine/BSA Nano-Carriers as the Efficient Targeted Anti-Cancer Drug Delivery System.
发表日期:2023 Aug 26
作者:
Hussein Nadhim Ghafil Al-Hasnawi, Vahid Pouresmaeil, Fatemeh Davoodi-Dehaghani, Sara Rahban, Aida Pouresmaeil, Masoud Homayouni Tabrizi
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
奎蒂亚宾(QTP)已被发现可抑制患有心理疾病的患者的癌症进展。本研究旨在制备叶酸连接的壳聚糖包覆奎蒂亚宾/牛血清白蛋白纳米载体(FCQB-NCs),并评估它们在前列腺、胰腺、结肠和乳腺癌细胞系上的抗氧化、凋亡和抗转移潜力。使用DLS、FESEM、FTIR和Zeta电位技术设计、制备和表征了FCQB-NCs。采用ABTS、DPPH和FRAP测定法研究了纳米载体的抗氧化活性。利用MTT测定法和基于qPCR的分析评估了FCQB-NCs的细胞毒性和凋亡/转移特性,分别测定了凋亡(Nf-KB)/转移(MMP2、MMP9和MMP13)基因的表达。采用AO/PI荧光细胞染色、DAPI染色和划痕试验方法验证了FCQB-NCs的凋亡和抗转移活性。51 nm的FCQB-NCs(PDI = 0.26)表现出抗氧化活性,并通过诱导Nf-KB过表达在选择性降低MDA-MB-231癌细胞的存活率,从而激活凋亡途径。此外,FCQB-NCs通过下调MMP2、MMP9和MMP13基因的表达,抑制了MDA-MB-231细胞的转移活性,通过检测减少的迁移率进行验证。FCQB-NCs选择性地诱导凋亡和抑制人乳腺癌细胞系的转移,这可以归因于QTP的两个主要(细胞外释放)和次要(细胞内释放)阶段的逐步释放。FCQB-NCs的高选择性细胞毒性影响可能是由于基于BSA和壳聚糖分子对QTP的两相捕获的新型逐步释放机制。因此,FCQB-NCs具有作为高效选择性抗乳腺癌药物的潜力。© 2023年,作者署名,独家许可给斯普林格科学+商业传媒有限责任公司,斯普林格自然出版集团的一部分。
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.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.