Geometric Engineering of BODIPY–Pt(II) Metallacycles: Balancing a Synergistic Nanoplatform for Photothermal, Photodynamic, and Immunotherapy

ABSTRACT The geometry of supramolecular coordination complexes (SCCs) is hypothesized to govern their photophysical properties and therapeutic outcomes, yet a semi‐quantitative framework linking molecular architecture to multimodal anticancer efficacy remains elusive. Herein, we construct a series of BODIPY–Pt(II) metallacycles with precisely defined triangular ( 60MBD ), quadrangular ( 90MBD ), and hexagonal ( 120MBD ) geometries and encapsulate them into F127 nanoparticles (NPs) to systematically investigate geometry‐dependent structure–property–function relationships. We uncover a geometry‐governed functional trade‐off: as the metallacycle size increases from triangular to hexagonal, the 1 O 2 quantum yield (Φ Δ ) progressively rises from 0.15% to 3.45%, while the photothermal conversion efficiency (PCE) concomitantly declines from 54.96% to 15.83%. Among the three geometries, triangular 60MBD NPs achieve the optimal balance in vitro and show markedly enhanced in vivo efficacy over the non‑cyclized counterpart. In a bilateral 4T1 tumor model, this optimized formulation achieves > 95% tumor inhibition upon NIR irradiation, potently induces immunogenic cell death, and promotes robust dendritic cell maturation and CD8 + T cell infiltration, leading to effective suppression of distant tumors. This work establishes a semi‐quantitative framework linking metallacycle geometry to trimodal therapeutic output and underscores geometric engineering as a powerful strategy for designing next‐generation cancer nanomedicines integrating photothermal, photodynamic, and immunotherapeutic modalities.