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.