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.本研究构建了一种巨噬细胞模拟纳米平台（macrophage-mimetic nanoplatform，MPMs@Cur-BDTA NPs），用于双模式干预。姜黄素可同时放大福斯特共振能量转移（Förster resonance energy transfer, FRET）以增强光疗效果，并抑制热休克蛋白70（heat shock protein 70, HSP-70）以破解肿瘤热防御机制。通过将姜黄素与精准调控的激发态动态发光体BDTA（excited-state dynamic luminogen BDTA）共沉淀，我们构建了用于能量再分配的协同FRET体系。在此构型下，姜黄素发挥双重功能：作为光子放大器，其可将光热转换效率提升至87.6%，并使单线态氧生成量提高1.7倍；作为生化调节剂，其可将HSP-70的表达水平下调50%，从而使胶质母细胞瘤细胞对热攻击更为敏感。这项以近红外成像（NIR imaging, NIR）为引导的三模态治疗策略（光热治疗/光动力治疗/化疗），在原位胶质母细胞瘤模型中将中位生存期从14.5天延长至19.4天。综上，本研究提出了一种全新的"能量通道劫持"与"分子防御解除"相结合的范式，重新定义了姜黄素这类天然分子如何主动调控脑肿瘤诊疗中的光治疗响应过程。