Immune/Hypoxic Tumor Microenvironment Regulation-Enhanced Photodynamic Treatment Realized by pH-Responsive Phase...

Area of Science:

• Nanomedicine
• Oncology
• Immunotherapy

Background:

• Triple-negative breast cancer (TNBC) lacks targeted therapy options due to specific receptor expression profiles.
• Current treatments for TNBC are often ineffective, highlighting the need for novel therapeutic strategies.
• Developing selective treatments and effective evaluation methods is crucial for advancing TNBC care.

Purpose of the Study:

• To fabricate a multifunctional, tumor-targeted nanosized ultrasound contrast nanobubble for TNBC therapy.
• To investigate the synergistic effects of photodynamic therapy (PDT) and PD-L1 checkpoint inhibition.
• To evaluate the potential of this nanoagent in reducing tumor-mediated immunosuppression and generating antitumor immunity.

Main Methods:

• Fabrication of a novel nanobubble loaded with chlorin e6 (Ce6), metformin (MET), and perfluorohexane (PFH), functionalized with anti-PD-L1 peptide (DPA-1).
• Utilizing the acidic tumor microenvironment to trigger PEG ligand detachment and expose DPA-1 for PD-L1 targeting.
• Assessing the combined therapeutic effects of PDT, metformin-induced hypoxia relief, and PD-L1 blockade.

Main Results:

• The nanobubble effectively targeted PD-L1 in the tumor microenvironment.
• Metformin administration reduced tumor hypoxia and enhanced Ce6-mediated PDT efficacy.
• The combination therapy demonstrated reduced tumor-mediated immunosuppression and induced significant antitumor immunity.

Conclusions:

• Multifunctional, tumor-targeted nanomedicine offers a promising strategy for TNBC treatment.
• The synergistic combination of PDT and PD-L1 blockade can overcome treatment resistance and enhance antitumor responses.
• This approach provides a new paradigm for developing advanced nanoagents against TNBC.