A mannose-functionalized pillar[5]arene-based supramolecular fluorescent probe for real-time monitoring of gemcitabine delivery to cancer cells

Abstract

The construction of a multifunctional nanodrug delivery system for the targeted delivery and real-time monitoring of nonfluorescent drugs has become one of the most important topics in cancer therapy. Herein, a novel supramolecular fluorescent probe (ManP5⊃G) for real-time monitoring of nonfluorescent drug gemcitabine (GEM) delivery to the cancer cells was constructed based on the host–guest interactions between the host molecule mannose-functionalized pillar[5]arene (ManP5) and a guest molecule (G) that is a near-infrared fluorescence receptor (dicyanomethylene-4H-pyran, DCM) derivative. ManP5⊃G self-assembles into nano-vesicles loaded with nonfluorescent anticancer drugs GEM to produce GEM@ManP5⊃G nanoparticles (NPs). The study results showed that GEM@ManP5⊃G NPs have good GSH responsiveness, achieving efficient delivery of GEM to cancer cells by mannose recognizing MCF-7 cells and selective release under GSH stimulation. Meanwhile, the fluorescence recovery of DCM stimulated by GSH can realize the real-time monitoring of GEM release. In addition, the GEM@ManP5⊃G NPs could effectively reduce the side effects of GEM on normal cells while improving the cancer cell damage capability. Therefore, the nanodrug delivery system constructed using the pillar[5]arene-based supramolecular fluorescent probe exhibits excellent capabilities of targeted drug delivery and the real-time monitoring of nonfluorescent drug release, which provides a novel approach to improve the efficacy of nonfluorescent drugs in enhancing chemotherapy.