Design of Raman tag-bridged core–shell Au@Cu3(BTC)2 nanoparticles for Raman imaging and synergistic chemo-photothermal therapy

Abstract

Nanoscale metal–organic frameworks (NMOFs) with ultrahigh porosities and incredibly high internal surface areas are potential nanomaterials to fabricate multifunctional theranostic platforms. This work describes the design of Raman tag-bridged core–shell nanoparticles (NPs) for multifunctional Raman imaging and chemo-phototherapy. Au@Cu₃(BTC)₂ NPs are characterized with the core of gold nanoparticles (Au NPs), the bridging of the Raman reporter molecule 4-mercaptobenzoic acid (4-MBA), and the shell of copper(II) carboxylate MOFs (Cu₃(BTC)₂). The preparation strategy is based on the assembly of Cu₃(BTC)₂ on Au NPs with the help of bifunctional 4-MBA. The Raman reporter molecule 4-MBA with characteristic Raman signals is involved in the linking of Au NPs and Cu₃(BTC)₂, avoiding additional modification of Raman reporter molecules and thus simplifying the synthesis process. Aptamers and the anti-cancer drug doxorubicin (DOX) were modified on Au@Cu₃(BTC)₂ for functionalization. The Au NP core not only acted as photothermal agents to produce hyperthermia for destroying cancer cells and promoting drug release, but also served as surface enhanced Raman scattering (SERS) substrates to enhance the Raman signal of 4-MBA. The Cu₃(BTC)₂ shell can provide sites for aptamer functionalization and drug loading. The Au@Cu₃(BTC)₂ NPs exhibited high drug loading capacity (57%) and good photothermal conversion efficiency. With good biocompatibility, high drug loading capacity, excellent SERS effect and photothermal effect, Au@Cu₃(BTC)₂ NPs showed effective theranostic applications in cell tracking and in vivo synergistic chemo-photothermal therapy of tumors, demonstrating the feasibility of theranostic applications in cancer diagnosis and therapy. It is speculated that this work would inspire further studies on the construction of theranostic nanoplatforms.