Rare earth fluorescent nanoprobes with minimal side effects enable tumor microenvironment activation for chemotherapy

Chemotherapy, the use of antitumor drugs to kill cancer cells, is currently one of the most effective treatments for cancer. However, serious toxic side effects caused by long-term drug accumulation can cause significant damage to the body, which limits the clinical application of antitumor drugs. In this study, a novel RENPs@DOX-Fe nanoprobe (NP) was constructed by coating the surface of rare earth nanomaterials (NaLuF4:Yb,Er) with a complex formed by doxorubicin (DOX) and iron ion (III). Due to the low toxicity of anthracycline-metal complexes, the damage to normal cells is reduced. The unique acidic microenvironment in tumor cells facilitates the decomposition and gradual release of DOX from the DOX–Fe complex. In addition, the DOX–Fe complex can convert near-infrared (NIR) light into heat energy, which promotes the decomposition of the complex, further enhancing the release of DOX in the tumor environment. The change of ratio fluorescence of rare earth nanomaterials at 660 and 1550 nm after DOX release enables visual monitoring of drug release, which can potentially improve the chemotherapeutic effect. In vitro experiments established that RENPs@DOX-Fe NPs with NIR illumination had good therapeutic efficacy in tumors. This work provides new insights into designing tumor microenvironment-responsive nanoprobes for chemotherapy with minimal side effects.