Bimodal silica nanoparticles co-doped with Mn²⁺and Ru²⁺complexes, variously conjugated with folates, for targeting...

The bimodality of amino-modified silica nanoparticles (SNs) manifested as an emission band with a maximum at 612 nm and relaxivity values r₁₍₂₎ of 17.7(30.3) mM^-1s^-1, was achieved by co-doping SNs with Mn²⁺ oxalate and [Ru(dipy)₃]²⁺ complex. Stepwise introduction of these dopants during the synthesis increases the manganese content and reduces the leaching of Mn²⁺ ions due to the electrostatic attraction of the cationic complex to oxalate. Conjugation of folate via amino groups provides both effective targeting and higher mobility of bimodal SNs during their uptake into cells. Formation of the protein corona (PC) plays a key role in the cellular uptake of these conjugated SNs, so their pre-coating with BSA affects both the targeting and mobility of these SNs. In an attempt to find a balance of targeting with increased mobility, folate-conjugated SNs were PEGylated by surface adsorption of F127 or PEG-300, while F127-based coating on unconjugated SNs enriched with folate-conjugated F127 molecules is an alternative attempt. The targeting effect is more pronounced and observed in a larger number of cancer cells when folate-conjugated nanoparticles are pre-coated with bovine serum albumin (BSA). However, this pre-coating slows the uptake of these nanoparticles by cells, whereas PEGylation accelerates cellular uptake, although it reduces the targeting effect of the nanoparticles. All this highlights that non-covalent surface modification of both folate-conjugated and unconjugated amine-modified manganese-doped silica nanoparticles is an effective tool for controlling their mobility and targeting.