A Novel Tumor-Penetrating Phosphorescent Nanoagent for Hypoxia-Activated NIR-II Bioimaging and Type-I PDT-Triggered...

Area of Science:

• Nanomedicine
• Biomedical Engineering
• Photodynamic Therapy

Background:

• Conventional photodynamic therapy (PDT) agents lack tumor specificity, limiting precision cancer treatment.
• Type-I PDT agents often exhibit
• always-on
• activity, leading to off-target effects.
• Developing targeted and image-guided therapeutic strategies is crucial for effective cancer therapy.

Purpose of the Study:

• To develop a novel tumor-penetrating phosphorescent nanoagent for hypoxia-activated near-infrared-II (NIR-II) bioimaging and type-I PDT.
• To enhance tumor specificity and therapeutic precision by combining advanced imaging with targeted therapy.
• To investigate the potential of this nanoagent to induce ferroptosis in cancer cells.

Main Methods:

• Synthesized iRGD-mediated organometallic complex nanoparticles (iPNs) utilizing a palladium-porphyrin complex (PdTCPP).
• Investigated hypoxia-activated NIR-II phosphorescence and intersystem crossing (ISC) properties of the nanoagent.
• Evaluated tumor penetration and tumor-to-normal tissue (T/NT) ratios using NIR-II bioimaging.
• Assessed type-I PDT efficacy by measuring reactive oxygen species (ROS) generation and analyzing ferroptosis and apoptosis pathways.

Main Results:

• The developed iPNs exhibited prominent ISC properties, enabling hypoxia-activated NIR-II phosphorescence and efficient type-I PDT.
• Conjugation with iRGD peptide significantly enhanced tumor penetration and achieved a 5-fold higher T/NT ratio compared to conventional probes.
• iPNs-triggered type-I PDT effectively induced intracellular superoxide and hydroxyl radical accumulation, inhibiting tumor growth.
• Proteomic analysis confirmed the activation of key ferroptosis and apoptosis pathways.

Conclusions:

• The developed organometallic complex nanoagent offers superior tumor specificity through hypoxia-activated NIR-II bioimaging.
• This nanoagent demonstrates significant potential for guiding precision type-I PDT to effectively induce ferroptosis and inhibit tumor progression.
• The combination of advanced imaging and targeted therapy represents a promising strategy for controllable cancer treatment.