Epitope Molecularly Imprinted Polymer Nanoparticles for Chemo-/Photodynamic Synergistic Cancer Therapy Guided by Targeted Fluorescence Imaging.

Abstract

It is a still tough task to precisely target cancer cells and efficiently improve the therapeutic efficacy of various therapies at the same time. Here, dual-template imprinting polymer nanoparticles (MIPs) with a core-shell structure were prepared, in which fluorescent silica nanoparticles (FSiO2) were the core and the imprinted polymer layers were the outermost shell. The imprinted layer was designed and constructed via free-radical precipitation approach on the surface of FSiO2, which simultaneously encapsulated gadolinium-doped silicon quantum dots and photosensitizers (Ce6). During the polymerization process, two template molecules were introduced into the mixtures, one was the epitope of CD59 protein (YNCPNPTADCK), which was overexpressed on the surface of a great deal of the solid cancers, and the other was antitumor agent doxorubicin (DOX) to be used for chemotherapy. Furthermore, the embedded Ce6 could generate toxic 1O2 under 655 nm laser irradiation to kill cancer cells, combining with the loaded-DOX to obtain a synergistic cancer therapy. Moreover, owing to the introduction of gadolinium-doped silicon quantum dots, Ce6, and DOX, the MIPs were endowed with targeted fluorescence imaging (FI) and MR imaging (MRI). In vitro and in vivo experiments had been conducted to demonstrate the excellent targeting ability and desirable treatment effect with negligible toxicity to healthy tissues and organs. As a consequence, the designed MIPs can promote the development of targeted recognition against biomarkers and precise treatment guided with cell imaging tools.