DataSheet1_Biodegradable hollowed mesoporous SeO2 nanoplatform loaded with indocyanine green for simultaneous NIR II fluorescence imaging and synergistic breast carcinoma therapy.docx

Contrast agents in the second window of the near-infrared region (NIR II, 1000–1700 nm) have several advantages and indocyanine green (ICG), which emits NIR II fluorescence, is clinically approved and its use has been widely investigated for in vivo imaging, specifically for delineating tumor outlines; however, insufficient tumor targeting and rapid physiological metabolism of free ICG has substantially impeded its further clinical application. Here, we constructed novel hollowed mesoporous selenium oxide nanocarriers for precise ICG delivery. After surface modification with the active tumor targeting amino acid motif, RGD (hmSeO2@ICG-RGD), the nanocarriers were preferentially targeted toward tumor cells and subsequently degraded for ICG and Se-based nanogranule release under tumor tissue extracellular pH conditions (pH 6.5). The released ICG acted as an NIR II contrast agent, highlighting tumor tissue, after intravenous administration of hmSeO2@ICG-RGD into mammary tumor-bearing mice. Importantly, the photothermal effect of ICG improved reactive oxygen species production from SeO2 nanogranules, inducing oxidative therapy. The synergistic therapeutic effects of hyperthermia and increased oxidative stress on 808 nm laser exposure induced significant tumor cell killing. Thus, our nanoplatform can generate a high-performance diagnostic and therapeutic nanoagent that facilitates in vivo tumor outline discrimination and tumor ablation.

在近红外区域（NIR II，1000-1700 nm）的第二窗口中，对比剂具有多重优势。吲哚氰绿（ICG），一种能够发出NIR II荧光的物质，已经获得临床批准，其应用于体内成像，特别是肿瘤轮廓的描绘方面，已被广泛研究；然而，由于肿瘤靶向性不足和游离ICG的快速生理代谢，其进一步的临床应用受到了显著阻碍。本研究中，我们构建了新型中孔硒氧化物空心纳米载体，以实现ICG的精确递送。经过具有肿瘤靶向活性的氨基酸序列RGD的表面修饰（hmSeO2@ICG-RGD），纳米载体优先靶向肿瘤细胞，并在肿瘤组织细胞外pH条件下（pH 6.5）降解，释放ICG和基于硒的纳米颗粒。释放的ICG作为NIR II对比剂，在hmSeO2@ICG-RGD经静脉注射到携带乳腺肿瘤的小鼠体内后，突出显示肿瘤组织。重要的是，ICG的光热效应提高了SeO2纳米颗粒产生的活性氧物种，从而引发氧化治疗。在808 nm激光照射下，高温和增加的氧化应激的协同治疗效应导致了显著的肿瘤细胞杀伤。因此，我们的纳米平台能够生成一种高性能的诊疗纳米剂，有助于体内肿瘤轮廓的识别和肿瘤消融。