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

被引:53
|
作者
Mishra, Snehasis [1 ,5 ]
Manna, Krishnendu [1 ]
Kayal, Utpal [2 ]
Saha, Moumita [1 ]
Chatterjee, Sauvik [2 ]
Chandra, Debraj [3 ]
Hara, Michikazu [4 ]
Datta, Sriparna [5 ]
Bhaumik, Asim [2 ]
Das Saha, Krishna [1 ]
机构
[1] Indian Inst Chem Biol, Canc Biol & Inflammatory Disorder Div, CSIR, 4 Raja SC Mullick Rd, Kolkata 700032, W Bengal, India
[2] Indian Assoc Cultivat Sci, Sch Mat Sci, 2A&B Raja SC Mullick Rd, Kolkata 700032, W Bengal, India
[3] Tokyo Inst Technol, Inst Innovat Res, World Res Hub Initiat WRHI, Midori Ku, Nagatsuta Cho 4259, Yokohama, Kanagawa 2268503, Japan
[4] Tokyo Inst Technol, Inst Innovat Res, Lab Mat & Struct, Midori Ku, Nagatsuta Cho 4259, Yokohama, Kanagawa 2268503, Japan
[5] Univ Calcutta, Dept Chem Technol, Kolkata 700009, W Bengal, India
关键词
NF-KAPPA-B; HEAT-SHOCK PROTEINS; SIGNALING PATHWAYS; DRUG-DELIVERY; OXIDE NANOPARTICLES; GOLD NANOPARTICLES; FACILE SYNTHESIS; DNA-DAMAGE; APOPTOSIS; CHEMOTHERAPY;
D O I
10.1039/d0ra00664e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 Fe(3)O(4)nanoparticles were embedded over the FA-functionalized QN-loaded monodisperse SBA-15 to prepare the highly orchestrated material FA-FE-SBA15QN. Thein vitroandin vivoanti-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. Thein vitroandin vivomagnetic 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.
引用
收藏
页码:23148 / 23164
页数:17
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