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
AbstractNaturally 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.
|Journal series||Oncotarget, ISSN 1949-2553|
|Publication size in sheets||1.2|
|Keywords in English||apoptosis, hepatocellular carcinoma, mesoporous silica nanoparticles, natural pro-drug, targeted drug delivery|
|Score||= 40.0, 18-08-2020, ArticleFromJournal|
|Publication indicators||= 16; = 23.0; : 2018 = 0.904; : 2016 = 5.168 (2) - 2016=5.312 (5)|
|Citation count*||25 (2020-08-27)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.