Synthesis of nanomedicines by nanohybrids conjugating ginsenosides with auto-targeting and enhanced MRI contrast for liver cancer therapy

Abstract

A new methodology has been developed with conjugating nanoparticles (NPs) with an active ingredient of Chinese herbs for nanomedicines with auto-targeting and enhanced magnetic resonance imaging (MRI) for liver cancer therapy. Fe@Fe₃O₄ NPs are first synthesized via the programed microfluidic process, whose surfaces are first modified with –NH₂ groups using a silane coupling technique that uses (3-aminopropyl)trimethoxysilane (APTMS) as the coupling reagent and are subsequently activated by the bifunctional amine-active cross-linker [e.g. disuccinimidyl suberate (DSS)]. The model medicines of ginsenosides pre-activated by APTMS are further cross-linked with activated NPs, forming the desired nanomedicines (Nano-Fe-GSS). Sizes and structures of Fe@Fe₃O₄ NPs were characterized by transmission electron microscopy and X-ray diffraction, revealing that their core-shell structures consist of amorphous boron doped Fe cores and partial crystalline Fe₃O₄ shells. The accomplishment of coupling reactions in the final nanomedicines is confirmed by the characterization of the composition of NPs and Nano-Fe-GSS via X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) spectroscopy. The nanoparticles’ effects as MRI contrast agents are further investigated by comparing the T₂ weighted spin echo imaging (T2WI) in livers before and after intravenous injection and intragastric administration of nanomedicines. The results indicate that these nanomedicines possess enhanced MRI effects. Investigation of the toxicity and metabolism of Nano-Fe-GSS suggests that they are safe to related vital organs. The results provide an efficient alternative route to synthesize desired multi-functional nanomedicines based on NPs and the active ingredients of Chinese herbs, which can promote their potential synergistic effects in anti-tumor therapy.

Keywords:

• Nanomedicine
• nanoparticles
• ginsenoside
• nanotoxicity
• cancer therapy

Acknowledgments

This work was supported by the National S&T Major Project [grant number 2018ZX10301201]; National natural science foundation of China [grant number 51371018 and 81372425]; and the Fundamental Research Funds for the Central University of China [grant number FRF-BR-14-001B].

Disclosure statement

No potential conflict of interest was reported by the authors.