Folic acid-hydrophilic polymer coated mesoporous silica nanoparticles target doxorubicin delivery

Abstract

Mesoporous silica nanoparticles (MSNs) gained significant attention, particularly in the pharmaceutical field. Folic acid (FA) shows marked promise as a targeting agent for its specific interaction with the folate receptor. This receptor is over-expressed on the cell surface of several cancerous cells like breast cancer. Polyethylene glycol (PE), as well as polypropylene glycol (PEG), is used to decorate nanoparticles to improve their biodistribution. Moreover, carboxymethyl beta-cyclodextrin (CM-β-CD), is used as a complexation molecule. In this study, we described the chemical synthesis, in vitro drug release and antiproliferative activity of doxorubicin-loaded/decorated MSNs further coupled with FA in two conditions: chemically bound or as a complex with CM-β-CD. Fourier Transform Infrared Spectroscopy with Transmission Electron Microscopy confirmed the successful surface change. Dynamic Light Scattering confirmed the change in surface characters like zeta potential, polydispersity index (PI), and size. PI improved from 0.58 to 0.23 while the size enlarged from 200 to 348 and 532 nm. Functionalized nanoparticles demonstrated more significant drug entrapment with (97%) while undecorated MSNs only showed (63%). Accordingly, we effectively synthesized FA-PEG2000-MSNs with IC₅₀: 0.015 mg/mL targeting HeLa cells. This approach may allow potential applications as a drug delivery system in cancer chemotherapy.

Highlights

• Mesoporous silica nanoparticles (MSNs) with a carboxylic acid or amine surface group can be successfully decorated with long-chain hydrophilic polymer via an amide bond.

• Carboxymethyl-β-cyclodextrin coupled with long-chain polymer as host to form a complex with targeting molecule folic acid.

• Folic acid can be anchored directly to a polymer coat.

• TEM; DLS and FTIR confirmed the surface modification.

• The drug encapsulation efficiency; cytotoxicity and selectivity of functionalized nanoparticles with PEG and conjugated with FA were the best.

• Chemical modification has improved cytotoxicity of doxorubicin and selectivity against Hela cells.

Graphical Abstract

Supplemental data for this article is available online at https://doi.org/10.1080/10837450.2021.1904258.

Keywords:

• Mesoporous
• silica nanoparticles
• carboxymethyl-β-cyclodextrin
• hydrophilic polymer
• folic acid
• doxorubicin
• breast cancer

Acknowledgments

The authors thank Hamdi-Mango Center for Scientific Research and the Deanship of Scientific Research at the University of Jordan for their generous funds.

Disclosure statement

No potential conflict of interest was reported by the author(s).