PEGMA-modified bimetallic NiCo Prussian blue analogue doped with Tb(III) ions: Efficiently pH-responsive and controlled release system for anticancer drug

Abstract

A novel drug nanocarrier system based on bimetallic NiCo Prussian blue analogue (NiCo-PBA) was constructed for targeted anticancer drug delivery and cancer therapy. Rare earth Tb3+ ion was doped in NiCo-PBA to prepare a complex with strong fluorescence performance (represented by NiCo-PBA@Tb3+). The NiCo-PBA@Tb3+ complex was functionalized with poly(ethyleneglycol)- dimethacrylate (PEGMA) (represented by NiCo-PBA@Tb3+@PEGMA) by the surface initiated atom transfer radical polymerization to enhance its aqueous stability, pH-responsive capability, and good biocompatibility, thus improving the drug-loading efficiency of NiCo-PBA. An aptamer ligand (AS1411) targeting nucleolin was insensitively anchored onto the NiCo-PBA@Tb3+@PEGMA surface for specifically recognizing breast cancer cells. Therefore, the functionalization of NiCo-PBA@Tb3+@PEGMA with AS1411 (denoted by NiCo-PBA@Tb3+@PEGMA@AS1411) allowed the pH-responsive drug release within cancer cells and enhanced the tumor-targeted delivery of doxorubicin (DOX). Confocal fluorescence imaging revealed that the NiCo-PBA@Tb3+@PEGMA@AS1411 composite was mainly located in the cytoplasm after cellular internalization, and released DOX within the cytoplasm. The in vivo antitumor study with tumor-bearing mice illustrated that NiCo-PBA@Tb3+@PEGMA@AS1411@DOX considerably accumulated in tumor tissues. The tumor growth can be effectively suppressed and exhibited enhanced an anticancer activity in vivo. The proposed NiCo-PBA@Tb3+@PEGMA@AS1411 composite represents a growing potential for effective DOX delivery and targeted therapy in vitro and in vivo. The present work can extend the application of PBAs in cancer therapy and cell imaging and provides a new strategy for the construction of controlled release system of anticancer drugs.