A Comprehensive Strategy Based on High Clinical Translational Nanosystem for Programmable Immunotherapy of Triple...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Triple-negative breast cancer (TNBC) is an immunologically "cold" tumor, resistant to monotherapies, with high recurrence and metastasis rates.
• Effective treatment requires reprogramming the tumor microenvironment (TME) from "cold" to "hot" to enhance therapeutic efficacy.

Purpose of the Study:

• To design and fabricate a multifunctional nanosystem (FeSH NPs) for synergistic photothermal-immunotherapy of TNBC.
• To evaluate the combined efficacy of photothermal therapy (PTT), TME reprogramming, and anti-PD-L1 antibody treatment.

Main Methods:

• Fabrication of FeSH NPs integrating a metal-polyphenol coordination complex for PTT and salvianolic acid B (SAB) as an immunomodulator.
• Utilizing photothermal/photoacoustic dual-mode imaging for guidance.
• Inducing immunogenic cell death (ICD) via PTT and releasing SAB to inhibit TGF-β and upregulate PD-L1 in the TME.
• Combining FeSH NPs treatment with anti-PD-L1 antibody therapy.

Main Results:

• FeSH NPs-mediated PTT induced ICD in TNBC.
• SAB release effectively remodeled the TME, inhibiting TGF-β and upregulating PD-L1.
• The combination therapy synergistically eradicated primary tumors, recurrence, and metastasis.
• FeSH NPs demonstrated good biosafety.

Conclusions:

• The developed FeSH NPs offer a promising strategy for programmed therapeutics in immunologically cold tumors like TNBC.
• This multifunctional nanosystem enables synergistic photothermal-immunotherapy, overcoming TNBC resistance and improving treatment outcomes.
• The approach holds high clinical translational potential for comprehensive cancer treatment.