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负载槲皮素的叶酸偶联磁性介孔二氧化硅纳米颗粒:一种癌症治疗的诊疗方法。

Folic acid-conjugated magnetic mesoporous silica nanoparticles loaded with quercetin: a theranostic approach for cancer management.

作者信息

Mishra Snehasis, Manna Krishnendu, Kayal Utpal, Saha Moumita, Chatterjee Sauvik, Chandra Debraj, Hara Michikazu, Datta Sriparna, Bhaumik Asim, Das Saha Krishna

机构信息

Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology 4, Raja S. C. Mullick Road Kolkata-700032 West Bengal India

Department of Chemical Technology, University of Calcutta Kolkata-700009 West Bengal India.

出版信息

RSC Adv. 2020 Jun 17;10(39):23148-23164. doi: 10.1039/d0ra00664e. eCollection 2020 Jun 16.

Abstract

The development of drug carriers based on nanomaterials that can selectively carry chemotherapeutic agents to cancer cells has become a major focus in biomedical research. A novel pH-sensitive multifunctional envelope-type mesoporous silica nanoparticle (SBA-15) was fabricated for targeted drug delivery to human colorectal carcinoma cells (HCT-116). SBA-15 was functionalized with folic acid (FA), and the material was loaded with the water-insoluble flavonoid, quercetin (QN). Additionally, acid-labile magnetite FeO nanoparticles were embedded over the FA-functionalized QN-loaded monodisperse SBA-15 to prepare the highly orchestrated material FA-FE-SBA15QN. The and anti-carcinogenic efficacy of FA-FE-SBA15QN was carried out to explore the pH-sensitive QN release with putative mechanistic aspects. FA-FE-SBA15QN caused a marked tumor suppression, and triggered mitochondrial-dependent apoptosis through a redox-regulated cellular signaling system. Furthermore, FA-IO-SBA-15-QN initiated the c-Jun N-terminal Kinase (JNK)-guided H2AX phosphorylation, which relayed the downstream apoptotic signal to the phosphorylate tumor suppressor protein, p53. On the other hand, the selective inhibition of heat shock protein-27 (HSP-27) by FA-FE-SBA15QN augmented the apoptotic fate through JNK/H2AX/p53 axis. The and magnetic resonance imaging (MRI) studies have indicated the theranostic perspective of the composite. Thus, the result suggested that the newly synthesized FA-FE-SBA15QN could be used as a promising chemo theranostic material for the management of carcinoma.

摘要

基于纳米材料的药物载体的开发,能够将化疗药物选择性地输送到癌细胞,这已成为生物医学研究的一个主要焦点。制备了一种新型的pH敏感多功能包膜型介孔二氧化硅纳米颗粒(SBA - 15),用于靶向输送至人结肠癌细胞(HCT - 116)。用叶酸(FA)对SBA - 15进行功能化修饰,并将水不溶性黄酮类化合物槲皮素(QN)负载到该材料上。此外,在FA功能化的负载QN的单分散SBA - 15上嵌入酸不稳定的磁铁矿FeO纳米颗粒,以制备高度有序的材料FA - FE - SBA15QN。对FA - FE - SBA15QN的抗癌功效进行了研究,以探索pH敏感的QN释放及其可能的机制。FA - FE - SBA15QN引起了显著的肿瘤抑制,并通过氧化还原调节的细胞信号系统触发线粒体依赖性凋亡。此外,FA - IO - SBA - 15 - QN引发了c - Jun N端激酶(JNK)介导的H2AX磷酸化,将下游凋亡信号传递给磷酸化的肿瘤抑制蛋白p53。另一方面,FA - FE - SBA15QN对热休克蛋白27(HSP - 27)的选择性抑制通过JNK/H2AX/p53轴增强了凋亡命运。体外和体内磁共振成像(MRI)研究表明了该复合材料的诊疗前景。因此,结果表明新合成的FA - FE - SBA15QN可作为一种有前途的化疗诊疗材料用于癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aba8/9054720/b94611e19163/d0ra00664e-s1.jpg

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