Dual-Pronged Strike: Curcumin Hijacks FRET Amplification and HSP-70 Sabotage in an NIR Phototheranostic Nanoplatform for Glioblastoma

This study presents a macrophage-mimetic nanoplatform (MPMs@Cur-BDTA NPs) for dual-mode intervention. Curcumin simultaneously amplifies Förster resonance energy transfer (FRET) to enhance phototherapy and inhibits heat shock protein 70 (HSP-70) to dismantle the thermal defense. By coprecipitating curcumin with a finely tuned excited-state dynamic luminogen BDTA, we establish synergistic FRET pairs for energy redistribution. Within this configuration, curcumin functions dually: as a photonic amplifier, it elevates the photothermal conversion efficiency to 87.6% and enhances singlet oxygen generation 1.7-fold; as a biochemical modulator, it downregulates HSP-70 expression by 50%, sensitizing glioblastoma cells to thermal attack. This triple-modal treatment strategy (photothermal therapy/photodynamic therapy/chemotherapy), guided by NIR imaging, extends the median survival time from 14.5 days to 19.4 days in orthotopic glioblastoma models. Collectively, this work introduces a new paradigm of "energy channeling hijacking" combined with "molecular defense disarmament", redefining how natural molecules like curcumin can actively orchestrate phototheranostic responses in brain tumor theranostics.