Folic acid–conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action
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Khaled AbouAitah1,2, Anna Swiderska-Sroda2, Ahmed A. Farghali3, Jacek Wojnarowicz2, Agata Stefanek4, Stanislaw Gierlotka2, Agnieszka Opalinska2, Abdou K. Allayeh5, Tomasz Ciach4 and Witold Lojkowski2
1Department of Medicinal and Aromatic Plants Research, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza, Egypt
2Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland
3Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt
4Biomedical Engineering Laboratory, Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, Poland
5Environmental Virology Laboratory, National Research Centre (NRC), Dokki, Giza, Egypt
Witold Lojkowski, email: [email protected]
Khaled AbouAitah, email: [email protected]
Keywords: mesoporous silica nanoparticles; hepatocellular carcinoma; targeted drug delivery; apoptosis; natural pro-drug
Received: February 23, 2018 Accepted: May 01, 2018 Published: May 29, 2018
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.
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