Photo-Driven Delivery of ¹²⁵I-Labeled Nanomicelles for Nucleus-Targeted Internal Conversion Electron-Based Cancer...

As a kind of high linear energy transfer (LET) radiation, internal conversion electrons are emitted from some radionuclides, such as ¹²⁵I, triggering severe DNA damage to tumor cells when transported into the nucleus. Herein, we develop a curcumin-loaded nanomicelle composed of a photosensitizer chlorin e6 (Ce6) and amphiphilic poly(ethylene glycol) (poly(maleic anhydride-alt-1-octadecene)-poly(ethylene glycol) (C₁₈-PMH-PEG)) to deliver ¹²⁵I into the nucleus under 660 nm laser irradiation, leading to the optimized imaging-guided internal conversion electron therapy of cancer. Ce6-containing nanomicelles (Ce6-C₁₈-PEG) self-assemble with nucleus-targeted curcumin (Cur), obtaining Ce6-C₁₈-PEG/Cur nanoparticles. After labeling Cur with ¹²⁵I, Ce6-C₁₈-PEG/Cur enables single-photon emission computed tomography and fluorescence imaging of the tumor, serving as a guide for follow-up laser irradiation. Notably, the 660 nm laser-triggered photodynamic reaction of Ce6 optimizes the delivery of Ce6-C₁₈-PEG/¹²⁵I-Cur at various stages, including tumor accumulation, cellular uptake, and lysosome escape, causing plenty of ¹²⁵I-Cur to enter the nucleus. By this strategy, Ce6-C₁₈-PEG/¹²⁵I-Cur showed optimal antitumor efficacy and high biosafety in mice treated with local 660 nm laser irradiation using efficient energy deposition of internally converted electrons over short distances. Therefore, our work provides a novel strategy to optimize ¹²⁵I delivery for tumor treatment.