A Nano-Electro-Platform Enabling Evolutionary Screening and Remodeling of Tumor Cells for Metastasis Inhibition.

Abstract

Tumor metastasis remains the leading cause of mortality among cancer patients. Addressing this challenge necessitates the development of effective strategies for targeted drug delivery and therapy. Given that metastatic lesions are primarily driven by highly aggressive tumor cell subpopulations, in-depth study of these cells and further guiding design of targeted therapeutics, play deterministic roles in metastasis inhibition. Herein, a nano-electro-platform is shown that enables non-invasive screening of aggressive cell subpopulations from heterogeneous tumor samples. Single-cell sequencing further reveals immune evasion pathways associated with their aggressive behavior. Targeting the screened aggressive cells, the platform implements a unique nanopore-focused electric field, which genetically remodels the cells to generate extracellular vesicles (EVs) with significantly enhanced tumor-targeting and therapeutic capabilities. The engineered EVs effectively activate macrophages and T cells, leading to robust tumor cell elimination and metastasis inhibition in lung cancer metastasis models. These highlight a versatile, multidisciplinary technique adopting a new path toward deep understanding and treating metastasis.