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Drug-device-field integration for mitochondria-targeting dysfunction and tumor therapy by home-tailored pyroelectric
Zhe Liu1, Yanxi Yang1, Xinru Kong1
1Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China; Tianjin Key Laboratory of Brain Science and Neural Engineering, Tianjin University, Tianjin, 300072, China.
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.
Insights
This study developed novel pyroelectric nanocomposites for advanced tumor treatment. This drug-device-field integration (DDFI) approach targets mitochondria, relieves hypoxia, and enhances anti-tumor efficacy, offering a promising new therapeutic pathway.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Hypoxia in the tumor microenvironment limits conventional cancer therapies.
- Mitochondria are key targets for inducing apoptosis and inhibiting tumor proliferation.
- Developing minimally invasive treatments with high efficacy is crucial for improved patient outcomes.
Purpose of the Study:
- To develop a pyroelectric nanocomposite for targeted tumor treatment.
- To integrate chemotherapy, photodynamic therapy, and physical fields for synergistic anti-tumor effects.
- To investigate the anti-tumor mechanisms, including immune response and mitochondrial dysfunction.
Main Methods:
- Layer-by-layer synthesis of Barium Titanate (BTO) based nanocomposites functionalized with polydopamine (PDA), Folic Acid (FA), Doxorubicin (DOX), and Epigallocatechin gallate (EGCG).
- Characterization of pyroelectric properties and drug-loading capacity.
- In vitro and in vivo evaluation of chemo-photodynamic therapy, hypoxia relief, and anti-tumor efficacy.
- Analysis of biomarkers related to mitochondria complexes and matrix metalloproteinases (MMPs) to elucidate anti-tumor mechanisms.
Main Results:
- The developed BTO@PDA-FA-DOX-EGCG nanocomposites demonstrated effective mitochondria targeting and hypoxia relief.
- The drug-device-field integration (DDFI) approach, combining chemotherapy, laser irradiation, and pyroelectric fields, significantly enhanced reactive oxygen species (ROS) production.
- Synergistic effects led to increased cell apoptosis and substantial tumor growth inhibition.
- Analysis revealed immune actuation and mitochondria dysfunction as key anti-tumor mechanisms.
Conclusions:
- Pyroelectric nanocomposites offer a novel platform for integrated cancer therapy.
- The DDFI strategy effectively overcomes tumor hypoxia and enhances therapeutic outcomes.
- This approach holds significant potential for developing advanced, minimally invasive cancer treatments.
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