In situ delivery of JPH203 via camptothecin-peptide conjugate nanoassemblies to trigger ferroptosis in triple-negative breast cancer - PubMed
6 hours ago
- #Triple-negative breast cancer
- #Nanoparticle drug delivery
- #Ferroptosis
- Triple-negative breast cancer (TNBC) lacks druggable targets and resists conventional therapies.
- Ferroptosis, an iron-dependent cell death mechanism, is a promising therapeutic target for TNBC.
- Solute carrier family 7 member 5 (SLC7A5) identified as a ferroptosis-suppressing prognostic target.
- Developed a tumor microenvironment-responsive camptothecin-peptide conjugate (CPC) nanoassembly for in situ JPH203 delivery.
- CPCs feature tumor-targeting motifs, a CPT-based hydrophobic core, and a gelatinase-cleavable linker for controlled release.
- JPH203 blocks leucine uptake, suppresses mTORC1, disrupts iron/redox homeostasis, and induces ferroptosis with 81.2% tumor suppression.
- CPCs-JPH activates dendritic cell maturation and CD8+ T-cell responses, improving survival in TNBC mouse models.
- The nanoplatform combines ferroptosis induction with immune system engagement for enhanced TNBC therapy.