Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines

The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and, secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption spectroscopy and microscopy. In addition, these systems have been tested against four different cancer cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show that the materials are more active when the quantity of folic acid is higher, especially in those cells that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show that a relatively high concentration of folic acid functionalization of the nanostructured silica together with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of membrane FR-α and by the release of intracellular FR-α. This study validates the potential use of a combination of mesoporous silica materials co-functionalized with folate targeting molecules and an organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing folate receptors.

Design, Synthesis, and Biological Activity of Releasable m-THPC-PEGfolate Conjugate Using a Disulfide-containing Linker

The present study reported the preparation of a novel mutual prodrug containing meso-tetra (m-hydroxy phenyl) chlorin (m-THPC), PEG and folate. The folate receptor (FR) targeting compound is a water-soluble chemical incorporating a hydrophilic PEG spacer unit and a reducible selfimmolative disulfide-based linker system between the FR-targeting ligand and the chlorin. The m- THPC-s-s-PEG-Folate was proved to release the parent drug and exhibited significant targeting effects on HeLa cells. In addition, the redox-responsive folate targeting photosensitizer m-THPC-s-s-PEG-Folate showed slightly higher phototoxicity than m-THPC-PEG-Folate for HeLa cells.

Zwitterionic shielded polymeric prodrug with folate-targeting and pH responsiveness for drug delivery

Zwitterionic polymers are a class of polymers that acts as both Lewis base and Lewis acid in solution.

Folate-targeting and bovine serum albumin-gated mesoporous silica nanoparticles as a redox-responsive carrier for epirubicin release

A targeted DDS with covalently conjugated BSA and folate for GSH-triggered drug release and recognition of FR-positive cancer cells.