Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Theranostics. 2022 Sep 21;12(15):6762-6778. doi: 10.7150/thno.77060. eCollection 2022.
Single imaging modality is still insufficient to evaluate the biological and anatomical structures of tumors with high accuracy and reliability. Generation of non-specific contrast, leading to a low target-to-background signal ratio, results in low imaging resolution and accuracy. Tumor environment-specific activatable multifunctional contrast agents need to maximize the contrast signals, representing a dual imaging-guided photothermal therapy (PTT) at target tumor sites. Cellular uptake, cytotoxicity assay, and photothermal conversion efficiency of MnCO-mineralized fluorescent polydopamine nanoparticles (MnCO-FPNPs) were evaluated using 4T1 breast cancer cells. dual-modality imaging was performed using IVIS imaging and a 4.7 T animal MRI systems after injection into 4T1 tumor-bearing nude mice. The effects of photothermal therapeutic through PTT were measured after irradiation with an 808 nm laser (1.5 W/cm) for 10 min, measuring the size of the tumors every 2 days. At physiological pH (7.4), MnCO-FPNP is efficiently quenched. Conversely, at acidic pH (5.4), the strong fluorescence (FL) is recovered due to the dissociation of Mn from the FPNPs. At pH 7.4, MnCO-FPNP activity is silenced to enhance water proton relaxation due to unionized MnCO maintenance; conversely, at acidic pH (5.4), MnCO-FPNPs efficiently release Mn ions, thereby resulting in -weighted magnetic resonance (MR) contrast enhancement. MnCO-FPNPs display a promising diagnostic ability for 4T1 breast cancer xenograft models, as well as exhibit a high photothermal conversion efficiency. A successful tumor treatment via their photothermal activity is accomplished within 14 days. Our studies exhibited unique "OFF-ON" activation abilities in FL/MR dual imaging and PTT functions. This approach suggests that the MnCO-FPNPs may serve as a useful platform for various mineralization-based multimodal imaging-guided PTT models for many cancer theranostic applications.
单一的成像模式仍然不足以高精度和高可靠性地评估肿瘤的生物和解剖结构。产生非特异性对比,导致靶标与背景信号的比值低,导致成像分辨率和准确性低。需要肿瘤环境特异性的可激活多功能对比剂来最大限度地提高对比信号,在靶肿瘤部位代表双重成像引导的光热治疗(PTT)。使用 4T1 乳腺癌细胞评估了 MnCO 矿化荧光聚多巴胺纳米粒子(MnCO-FPNP)的细胞摄取、细胞毒性测定和光热转换效率。将 MnCO-FPNP 注入 4T1 荷瘤裸鼠后,使用 IVIS 成像和 4.7 T 动物 MRI 系统进行了双模式成像。在使用 808nm 激光(1.5W/cm)照射 10 分钟后,通过测量肿瘤的大小来测量光热治疗的效果,每 2 天测量一次。在生理 pH 值(7.4)下,MnCO-FPNP 被有效地猝灭。相反,在酸性 pH 值(5.4)下,由于 Mn 从 FPNP 中解离,强荧光(FL)得到恢复。在 pH 值为 7.4 时,MnCO-FPNP 的活性被沉默,以增强由于未离解的 MnCO 维持而导致的水质子弛豫;相反,在酸性 pH 值(5.4)下,MnCO-FPNP 有效地释放 Mn 离子,从而导致 T1 加权磁共振(MR)对比增强。MnCO-FPNP 对 4T1 乳腺癌异种移植模型具有有前途的诊断能力,并表现出高的光热转换效率。通过它们的光热活性成功地在 14 天内完成了肿瘤治疗。我们的研究在 FL/MR 双成像和 PTT 功能方面表现出独特的“开启-关闭”激活能力。这种方法表明,MnCO-FPNP 可能作为一种有用的平台,用于多种基于矿化的多模态成像引导的 PTT 模型,用于许多癌症治疗应用。
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