Oxygen-Adaptive Covalent Organic Framework Nanoarchitectonics with High Photothermal Conversion Efficiency for...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• The tumor microenvironment (TME) presents challenges for cancer therapy due to varying oxygen levels (normoxia and hypoxia).
• Oxygen-adaptive nanomedicines are needed for effective multimodal therapy in complex TME.
• Covalent organic frameworks (COFs) offer potential as versatile nanoplatforms.

Purpose of the Study:

• To develop an oxygen-adaptive nanoplatform, GTPZ, for quadruple-modal synergistic cancer therapy.
• To investigate GTPZ's ability to integrate chemodynamic therapy (CDT), photothermal therapy (PTT), photodynamic therapy (PDT), and hypoxia-activated chemotherapy.
• To evaluate GTPZ's dynamic oxygen-adaptive capabilities within the TME.

Main Methods:

• GTPZ, a COF-based nanoplatform, was synthesized and characterized.
• Quadruple-modal therapy was integrated: CDT, PTT, Type I/II PDT, and hypoxia-activated chemotherapy (tirapazamine, TPZ).
• Oxygen-adaptive PDT switching (Type II in normoxia, Type I in hypoxia) and TPZ release were studied.
• In vitro and in vivo experiments using MCF-7 models were conducted to assess tumor suppression.

Main Results:

• GTPZ demonstrated a record 72% photothermal conversion efficiency among COF nanomedicines.
• Spatiotemporal control over hypoxia-activated tirapazamine (TPZ) release was achieved.
• GTPZ exhibited dynamic oxygen-adaptive PDT, switching between Type I and Type II based on oxygen gradients.
• Phototherapy-induced oxygen depletion amplified TPZ activation.
• High tumor suppression was observed in MCF-7 models via synergistic lipid peroxidation, cell cycle arrest, and ferroptosis.

Conclusions:

• GTPZ is an effective oxygen-adaptive nanoplatform for quadruple-modal synergistic cancer therapy.
• The nanoplatform dynamically adapts to TME oxygen gradients, enhancing therapeutic efficacy.
• This work presents a paradigm for designing intelligent nanomedicines for complex tumor environments.