PEG-templated mesoporous silica nanoparticles exclusively target cancer cells

Abstract

Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug delivery carriers, as well as efficient tools for fluorescent cell tracking. The major limitation is that MSNs enter cells regardless of a target-specific functionalization. Here we show that non functionalized MSNs, synthesized using a PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a highly specific, receptor mediated, cellular internalization of folic acid (FOL) grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing cells. Neither the classical clathrin pathway nor macropinocytosis is involved in the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated with MSN-FOL-Cp. The results presented here show that our mesoporous nanoparticles do not enter cells unless opportunely functionalized, suggesting that they could represent a promising vehicle for drug targeting applications.

Cellular endocytosis and trafficking of cholera toxin B-modified mesoporous silica nanoparticles

“…10 These tactics have shown partial success in increasing the delivery of therapeutic agents from MSNs. 1, 7, 8, 11, 12 Nevertheless, another way to enhance the efficacy of MSNs as drug delivery system is by modifying their trafficking pathway inside the cells. By delivering the active compounds in specific compartments such as cytosol, nucleus or mitochondria the effect of the therapeutic agents can be enhanced.…”

Colloidal and spherical mesoporous silica particles: synthesis and new technologies for delivery applications

“…Finally, other SDAs besides CTAB are also reported in the literature to produce mostly amine-functionalized MSP. The use of anionic PMES [109], nonionic Triton X-100 [110] and Pluronic P123 [44], F127 [57,69] or F-38 [91] lead however to particles of bigger sizes from 100 nm to 2 lm. The usual broad dispersions obtained from these MSP and their not well-defined morphologies raise many technological challenges and open up new possibilities for the development and use of these alternative mesoporous materials in DDS applications.…”

The role of surface functionalization of silica nanoparticles for bioimaging

“…1,11 SNP surface can be functionalized by distinct types of systems of relevance for biointeractions, such as antibodies, folic acid, aptamers, PEG, carbohydrates, lipids, amongst others. 15,[90][91][92] Covalent functionalization at the silica surfaces is possible by the well-established silane chemistry, mediating strong linkages between the SNP surface and selected biomolecules. 93,94 A large library of commercially available halosilanes and alkoxysilanes is currently available, allowing the introduction of functional groups like amines, carboxylates, epoxides and thiols.…”