Folic acid-conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action

Khaled AbouAitah , Anna Świderska-Środa , Ahmed A. Farghali , Jacek Wojnarowicz , Agata Stefanek , Stanisław Gierlotka , Agnieszka Opalinska , Abdou K. Allayeh , Tomasz Ciach , Witold Łojkowski

Abstract

Naturally derived prodrugs have a wide range of pharmacological activities, including anticancer, antioxidant, and antiviral effects. However, significant barriers inhibit their use in medicine, e.g. their hydrophobicity. In this comprehensive study, we investigated simple and effective nanoformulations consisting of amine-functionalized and conjugated with folic acid (FA) mesoporous silica nanoparticles (MSNs). Two types of MSNs were studied: KCC- 1, with mean size 324 nm and mean pore diameter 3.4 nm, and MCM - 41, with mean size 197 and pore diameter 2 nm. Both types of MSNs were loaded with three anticancer prodrugs: curcumin, quercetin, and colchicine. The nanoformulations were tested to target in vitro human hepatocellular carcinoma cells (HepG2) and HeLa cancer cells. The amine-functionalized and FA-conjugated curcumin-loaded, especially KCC-1 MSNs penetrated all cells organs and steadily released curcumin. The FA-conjugated MSNs displayed higher cellular uptake, sustained intracellular release, and cytotoxicity effects in comparison to non-conjugated MSNs. The KCC-1 type MSNs carrying curcumin displayed the highest anticancer activity. Apoptosis was induced through specific signaling molecular pathways (caspase-3, H2O2, c-MET, and MCL-1). The nanoformulations displayed also an enhanced antioxidant activity compared to the pure forms of the prodrugs, and the effect depended on the time of release, type of MSN, prodrug, and assay used. FA-conjugated MSNs carrying curcumin and other safe natural prodrugs offer new possibilities for targeted cancer therapy.
Author Khaled AbouAitah - [National Research Centre]
Khaled AbouAitah,,
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, Anna Świderska-Środa - Instytut Wysokich Ciśnień Polskiej Akademii Nauk (Instytut Wysokich Ciśnień Polskiej Akademii Nauk) [High Pressure Research Center of the Polish Academy of Sciences]
Anna Świderska-Środa,,
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, Ahmed A. Farghali - [Beni-Suef University]
Ahmed A. Farghali,,
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, Jacek Wojnarowicz - [High Pressure Research Center of the Polish Academy of Sciences]
Jacek Wojnarowicz,,
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, Agata Stefanek (FCPE / DBBE)
Agata Stefanek,,
- Department of Biotechnology and Bioprocess Engineering
, Stanisław Gierlotka - [High Pressure Research Center of the Polish Academy of Sciences]
Stanisław Gierlotka,,
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, Agnieszka Opalinska - [High Pressure Research Center of the Polish Academy of Sciences]
Agnieszka Opalinska,,
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, Abdou K. Allayeh - [National Research Centre]
Abdou K. Allayeh,,
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, Tomasz Ciach (FCPE / DBBE)
Tomasz Ciach,,
- Department of Biotechnology and Bioprocess Engineering
, Witold Łojkowski - Instytut Wysokich Ciśnień Polskiej Akademii Nauk (Instytut Wysokich Ciśnień Polskiej Akademii Nauk) [High Pressure Research Center of the Polish Academy of Sciences]
Witold Łojkowski,,
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Journal seriesOncotarget, ISSN 1949-2553, (A 40 pkt)
Issue year2018
Vol9
No41
Pages26466-26490
Publication size in sheets1.2
Keywords in Englishapoptosis, hepatocellular carcinoma, mesoporous silica nanoparticles, natural pro-drug, targeted drug delivery
ASJC Classification2730 Oncology
DOIDOI:10.18632/oncotarget.25470
URL http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=25470&path%5B%5D=79756
Languageen angielski
File
AbouAitah, K. (i in.) - Folic acid-conjugated...pdf 6.63 MB
Score (nominal)40
ScoreMinisterial score = 40.0, 05-09-2019, ArticleFromJournal
Publication indicators Scopus Citations = 4; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.039; WoS Impact Factor: 2016 = 5.168 (2) - 2016=5.312 (5)
Citation count*8 (2019-09-08)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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