Metal–organic framework-based pH/NIR dual-responsive nanoparticles for combined photothermal/photodynamic therapy and chemotherapy of cancer

Abstract

Metal–organic frameworks (MOFs) are unique coordination polymers that have emerged as important candidates for drug delivery in recent years. Herein, we designed a drug delivery system for multi-modal combination therapy (IR-820/DOX@MIL-101-PDA-PEG-F3, simplified as ID@MIL-PPF3). In this study, pH-sensitive nanocarriers MIL-101(Fe) were prepared and loaded with the effective chemotherapy agent doxorubicin (DOX) and the phototherapeutic reagent new indocyanine green (IR-820) using a physical adsorption method. Dopamine was spontaneously polymerized in alkaline solutions to form a hybrid coating on MIL-101(Fe) (denoted as ID@MIL-101-PDA). The surface of ID@MIL-101-PDA was functionalized by the synthesized polymer NH₂-PEG-OCH₃/F3 to obtain ID@MIL-PPF3. Characterization results show that ID@MIL-PPF3 has a good drug loading rate (27.7%) and photothermal conversion efficiency (28.89%). In addition, Fe³⁺ released from MIL-101(Fe) can engage in a Fenton-like reaction to generate hydroxyl radicals (˙OH) to realize chemodynamic therapy (CDT). ID@MIL-PPF3 not only demonstrates the ability to intelligently release drugs, but also realizes chemotherapy combined with PDT/PTT/CDT therapy for tumor cells, which was proved by in vitro evaluation. In conclusion, ID@MIL-PPF3 provides a new idea and method for building a multi-modal combination therapy targeted drug delivery platform.