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

Abstract

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.

Au–ZnO Nanomatches as Radiosensitizers with Improved Reactive Oxygen Species Generation and Tumor Hypoxia Modulation for Enhanced Radiotherapy on Triple-Negative Breast Cancer

“…4T1 cells showed increased TUNEL positive signals after 4 Gy X-ray irradiation with AZ, indicating the enhanced DNA damage (Figure d) . γ-H2AX is a marker used to confirm DNA DSBs. , Figure e displays that 4T1 cells treated with AZ also showed higher γ-H2AX expression, which means that AZ induces DNA DSBs in 4T1 cells following RT.…”

“…47 γ-H2AX is a marker used to confirm DNA DSBs. 48,49 Figure 3e displays that 4T1 cells treated with AZ also showed higher γ-H2AX expression, which means that AZ induces DNA DSBs in 4T1 cells following RT.…”

Development of Small HN Linked Radionuclide Iodine-125 for Nanocarrier Image Tracing in Mouse Model

“… 36 Similarly, Qin et al reported a nucleus-targeted internal conversion electron-based cancer therapy strategy induced by nanomicelles, which was labeled by radionuclide 125 I after the PEG modification on its surface. 37 Thus, it is evident that the radionuclide 125 I labeling method for NCs employing corresponding ligand design cannot be replicated and applied on a large scale. Therefore, it is necessary to establish a more universal radiolabeling method for NCs.…”

Targeting the organelle for radiosensitization in cancer radiotherapy

“…A recent study by Qin group [92] developed Ce6-C 18 -PEG/ 125 I-Cur nano-micelles, amphiphilic poly (maleic anhydride-alt-1-octadecene)-poly (ethylene glycol) (C 18 -PMH-PEG) was grafted with the photosensitizer chlorin e6 (Ce6) to form nano-micelles (Ce6-C 18 -PEG). Then Ce6-C 18 -PEG was combined with the nucleus targeting substance curcumin (Cur), self-assembling to obtain Ce6-C 18 -PEG/Cur nanoparticles, which showed the ability to block the cellular mass exchange and promoting program cell death [93] .…”