A self-assembled metal-polyphenolic nanomedicine for mild photothermal-potentiated chemodynamic therapy of tumors

•Coordination of FeII and EGCG endows FeEP-NPs with superior photothermal property.•The FeEP-NPs possess photothermal enhanced •OH generation capability.•The sustained supply of FeII in Fenton reaction achieves stable •OH production.•Partly released EGCG inhibits cellular HSP expression for enlarged mild-PTT.•FeEP-NPs show synthesis simplification and functional integration for tumor therapy. Engineering nanotherapeutics with simple ingredients but multiple functions at large-scale via easy methods is still a formidable challenge for cancer treatment. Herein, a novel multifunctional nanotherapeutic agent (named as FeEP-NP) was fabricated by a one-pot self-assembly method based on the coordination between FeII and (-)-epigallocatechin gallate (EGCG) with poly(vinylpyrrolidone) serving as a stabilizer. The designed FeEP-NPs could produce the toxic hydroxyl radical (•OH) effectively via Fenton reaction for chemodynamic therapy (CDT). Intriguingly, the unique binding between EGCG and FeII ions endows nanoparticles with strong absorption and photothermal conversion capabilities in the near-infrared (NIR) region, which could achieve mild hyperthermia-enhanced CDT under NIR laser irradiation. More impressively, the partially released EGCG could accelerate the FeIII/FeII conversion to augment the generation of •OH to further promote CDT, and simultaneously down regulate the intracellular expression of heat shock protein 90 (HSP 90) to enhance mild photothermal therapy (PTT). Both in vitro and in vivo results demonstrate that the low-temperature PTT-potentiated CDT based on FeEP-NPs could suppress tumors more efficiently. Overall, this work presents a novel multifunctional nanoplatform with succinct design, highlighting significant prospects for future clinical application. [Display omitted]