Multifunctional hollow CaF2:Yb3+/Er3+/Mn2+-poly(2-Aminoethyl methacrylate) microspheres for Pt(IV) pro-drug delivery and tri-modal imaging

Abstract

Combining the multi-modal medical imaging with cancer therapy in one single system has attracted the great interests for theranostic purpose. In this paper, CaF2:Yb3+/Er3+/Mn2+-poly(2-Aminoethyl methacrylate) (UCHNs-PAMA) hybrid microspheres were successfully fabricated. The synthetic route to the nanocomposite based on a facile hydrothermal method for fabrication of hollow upconversion (UC) nanospheres at first and then post-filling the PAMA interiorly through photo-initiated polymerization. The UCHNs showed orange fluorescence under 980 nm near infrared (NIR) laser excitation, which provided the upconverting luminescence (UCL) imaging modality. Meanwhile, the presence of functional Mn2+ and Yb3+ offered the enhanced T1-weighted magnetic resonance (MR) and computed tomography (CT) imaging, respectively. Thanks to introducing amine groups-containing PAMA inside the hollow nanospheres, the Pt(IV) pro-drug, c,c,t-Pt(NH3)2Cl2(OOCCH2CH2COOH)2 (DSP), can be conveniently bonded on the polymer network to construct a nanoscale anti-cancer drug carrier. The UCHNs-PAMA-Pt(IV) nanocomposite shows effective inhibition for Hela cell line via MTT assay. In contrast, Pt(IV) pro-drug and UCHNs-PAMA microspheres behave little cytotoxicity to Hela cells. This should be attributed the fact that the anti-cancer ability can be recovered only when Pt(IV) pro-drug was reduced to Pt(II)-drug in cellular environment. Furthermore, the in vivo experiments on small mice also confirm that the hybrid microspheres have relatively low toxic side effects and high tumor inhibition rate. These findings show that the multifunctional hybrid microspheres have potential to be used as UCL/MR/CT tri-modal imaging contrast agent and anti-cancer drug carriers.