Facile synthesis of highly biocompatible folic acid-functionalised SiO2 nanoparticles encapsulating rare-earth metal complexes, and their application in targeted drug delivery

Abstract

Mesoporous silica core–shell nanospheres encapsulating a rare-earth metal complex (RC) were first synthesised through a facile W/O (water in oil) inverse microemulsion method. In order to achieve targeted complex delivery, folic acid (FA) was used as the targeting component due to its high affinity for over-expressed folate receptors (FRs) in cancer cells. The RC₂@SiO₂-FA nanospheres were characterised via ultraviolet-visible light absorption spectroscopy (UV-vis spectroscopy), dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A microwave method was used to synthesise five RC cores based on 4-chlorophenoxyacetic acid, and their crystal structures were further confirmed using X-ray diffraction. The five RC cores have the following chemical formulae: [Er₂(p-CPA)₆(H₂O)₆] RC₁, [Ho₂(p-CPA)₆(H₂O)₆] RC₂, [Sm(p-CPA)₃(H₂O)] RC₃, [Pr(p-CPA)₃(H₂O)]·3H₂O RC₄ and [Ce(p-CPA)₃(H₂O)₂]·2H₂O RC₅. The carboxyl groups showed two kinds of coordination modes, namely μ₂–η¹:η¹ and μ₂–η¹:η², among RC₁–RC₅. The flexible –OCH₂COO– spacer group, which can undergo rotation of its C–O and C–C bonds, offered great potential for structural diversity. In vivo experiments revealed that the nanospheres exhibited no obvious cytotoxicity on HepG2 cells and 293 T cells, even at concentrations of up to 80 μg mL⁻¹. Nevertheless, all of the RC cores showed a certain degree of anti-tumour efficacy; in particular, RC₂ showed the strongest cytotoxicity against HepG2 cells. Interestingly, the cytotoxicity of all of the RC₂@SiO₂-FA nanospheres was higher than that of lone RC₂. These types of FA-targeted mesoporous silica nanocarriers can be used for the delivery of anti-tumour RC, and provide a basis for the further study of affordable non-platinum-based complexes.