Intracellular Metal-Organic Frameworks: Integrating an All-In-One Semiconductor Electrode Chip for Therapy, Capture, and Quantification of Circulating Tumor Cells

Capture, analysis, and inactivation of circulating tumor cells (CTCs) have emerged as important issues for the early diagnosis and therapy of cancer. In this study, an all-in-one sensing device was developed by integrating magnetic metal-organic framework (magMOF) nano-particles (NPs) and TiO2 nanotube arrays (TiNTs). The magMOF NPs are composed of a magnetic Fe3O4 core and a MIL-100(Fe) shell, which is loaded with glucose oxidase (GOD) and provides an intensive starvation therapy by catalyzing the consumption of cellular nutrients, thus accelerating the generation of intracellular iron ions by MIL-100(Fe) dissolution. Importantly, these iron ions not only lead to an intensive Fenton-like reaction but also establish an excellent correlation of electrochemical intensities with cancer cell numbers. Owing to the intracellular magMOF NPs, the CTCs were magnetically collected onto TiNTs. The exogenous center dot OH radicals generated by TiNT photocatalysis trigger iron ions to be rapidly released out and subsequently detected via differential pulse voltammetry using TiNTs as the electrode. An excellent correlation of differential pulse voltammetry intensities with CTC numbers is obtained from 2 to 5000 cell mL(-1). This nanoplatform not only paves a way to combine starvation therapy agents with Fenton-like reaction for chemodynamic therapy but also opens up new insights into the construction of all-in-one chips for CTC capture and diagnosis.