Adapting and Remolding: Orchestrating Tumor Microenvironment Normalization with Photodynamic Therapy by Size...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Abnormal tumor microenvironment (TME) hinders cancer treatment by promoting tumor growth and metastasis.
• Physiological barriers within the TME impede effective drug delivery, presenting a significant challenge in oncology.

Purpose of the Study:

• To design and evaluate a size-transformable nanoframework (T-PFRT) for remodeling the TME.
• To enhance photodynamic therapy (PDT) efficacy by overcoming TME-related barriers for cancer treatment.

Main Methods:

• Developed a core-satellite nanoframework (T-PFRT) responsive to matrix metalloproteinase 2 (MMP2).
• The core contains a TGFβ inhibitor and hemoglobin for stroma remodeling and hypoxia relief.
• Satellite particles encapsulate photosensitizers for deep tumor penetration and oxygen-fueled PDT.

Main Results:

• T-PFRT successfully dissociated in the TME, remodeling the tumor stroma and alleviating hypoxia.
• The nanoframework facilitated the penetration of photosensitizers to deep tumor tissues.
• Achieved significant inhibition of primary and metastatic tumor growth through enhanced PDT.

Conclusions:

• The T-PFRT nanoframework effectively overcomes TME barriers, including stroma and hypoxia.
• This adaptable nanotherapy demonstrates potent therapeutic outcomes for primary and metastatic cancers.
• T-PFRT offers a promising strategy for augmenting photodynamic therapy in cancer treatment.