Carrier-Free Nanoparticles Enhance Photothermal-Immune Therapy via Metabolic Reprogramming in Triple-Negative Breast...

Area of Science:

• Nanomedicine
• Oncology
• Immunotherapy

Background:

• Triple-negative breast cancer (TNBC) presents significant therapeutic challenges.
• Reprogramming tumor metabolism offers a novel strategy to enhance treatment efficacy.
• Photothermal therapy (PTT) shows promise but requires optimization for potent anti-tumor effects.

Purpose of the Study:

• To develop a carrier-free co-assembled nanoplatform (IR@PF-M NPs) for enhanced photothermal-immunotherapy against TNBC.
• To investigate the synergistic effects of PTT and methionine metabolism reprogramming.
• To evaluate the dual-targeting and immunomodulatory capabilities of the nanoplatform.

Main Methods:

• Co-assembly of a methionine adenosyltransferase 2A (MAT2A) inhibitor (PF9366) with a near-infrared (NIR) dye (IR808), followed by surface modification with DSPE-PEG2000-Met.
• Utilized enhanced permeability and retention (EPR) effect and methionine transporter targeting for dual tumor accumulation.
• Investigated NIR-induced photothermal effects, immunogenic cell death (ICD), and methionine metabolism disruption.

Main Results:

• IR@PF-M NPs demonstrated enhanced intratumoral accumulation and photothermal efficiency upon NIR irradiation.
• NIR irradiation induced significant photothermal effects (>50°C), triggering ICD and an immune-activated tumor microenvironment.
• PF9366 disrupted methionine metabolism, amplifying ICD and suppressing TNBC progression and metastasis.
• The integrated approach showed superior antitumor efficacy and immunomodulatory activity.

Conclusions:

• The developed IR@PF-M NPs effectively integrate PTT with metabolic intervention for synergistic anti-TNBC effects.
• The nanoplatform exhibits dual targeting and reprogramming of methionine metabolism for enhanced therapeutic outcomes.
• IR@PF-M NPs represent a promising strategy for TNBC management by converting the tumor microenvironment into an immune-hot state.