Drug-device-field integration for mitochondria-targeting dysfunction and tumor therapy by home-tailored pyroelectric nanocomposites

Abstract

In spite of the hypoxia tumor microenvironment, an efficacious treatment with minimal invasiveness is highly desirable. Among common cellular organelles, mitochondria is a common target for inductive cellular apoptosis and tumor proliferation inhibition. Nevertheless, tumor hypoxic circumstances always give rise to poor therapeutic efficiency and instead lead to lesion recurrence and unsatisfactory prognosis. Herein, a home-tailored pyroelectric nanocomposites of BTO@PDA-FA-DOX-EGCG have been developed via a layer-by-layer synthesis to serve a cutting-edge tumor treatment with specific mitochondria-targeting, hypoxia-relieving, chemo-photodynamic performance and high anti-tumor efficacy. In particular, this therapeutic modality is featured as drug-device-field integration (DDFI) by combining chemo-drugs of DOX and EGCG, a commercially available medical laser and physical pyroelectric fields, which synergistically contributed to continuing ROS production and consequently cell apoptosis and tumor growth inhibition. Meanwhile, an anti-tumor mechanism of immune actuation and mitochondria dysfunction was elucidated by analyzing specific biomarkers of mitochondria complexes and MMPs, and therefore this research opened up a potential pathway for advanced tumor treatment by incorporating nanocomposites, medical devices and physical fields in a DDFI manner.