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

作者：Jinnan Huo, Qiang Zhang, Mingbo Zhang, Jiaxin Shi, Wenqi Zhang, Liying Han, Yuanyuan Li, Xi Wu, Mengnan Jia, Ying Zheng, Ying Meng, Tianjiao Li, Shuai Wang, Yongrui Bao, Xiansheng Meng · 发表于：Journal of Medicinal Chemistry · 年份：2025 · DOI：10.1021/acs.jmedchem.5c01274 · 被引用次数：4 · 研究领域：Nanoplatforms for cancer theranostics、RNA Interference and Gene Delivery、Nanoparticle-Based Drug Delivery

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.