通过靶向酸性肿瘤微环境（TME）的MR纳米探针为体内癌症成像提供了巨大潜力。然而，其成像精准性受肿瘤部位延迟响应及不可控的背景噪声限制。
近日，上海交通大学王中领教授和南京医科大学康达学院李蕾副教授等人在Science China Materials发表研究论文，构建了一种酸性微环境响应纳米探针SPIO@ZIF-8@Gd（SZG），该探针可快速响应于肿瘤酸性微环境变化，具有T1-T2双激活效应。
本文要点
1) SZG探针在生理条件下T1和T2信号对比度降低，而靶向TME，沸石咪唑酯骨架-8（ZIF-8）层将快速分解，释放Gd3+（T1WI），并暴露SPIO核心（T2WI），从而实现T1和T2双激活效应。2) 与之前报道的T1-T2双响应纳米探针相比，SZG纳米探针在酸性条件下30分钟可呈现出显著的“双激活”效应，4小时后达到激活峰值。此外，其弛豫时间与pH值间具有良好的相关性。3) 当SZG纳米探针与“双对比增强减影（DESI）”联合使用，可将正常组织与病变组织间的对比度差异提高10倍，这显著高于传统的T1/T2单模对比剂。以上研究结果显示通过抑制背景噪声的T1-T2双激活成像策略，为精准肿瘤恶性程度鉴别、早期检测和准确分级提供了新思路。Figure 1. Schematic illustration of the fabrication and applications of the pH-responsive T1 and T2 dual-activation contrast agent.Figure 2. Characterization of SZG and its T1&T2 dual-quenching properties. (a, b) Representative TEM micrograph (a) and diameter distributions (b) of the SZG nanoparticles. (c, d) Representative TEM micrograph (c) and diameter distributions (d) of the SZG nanoparticles treated with pH (5.0) for 6 h. (e) EDX element mapping images of SZG for Fe, Zn, and Gd. Representative data are shown from two independently repeated experiments. Scale bar: 20 nm. (f, h) T1- weighted MR images (f) and the linear fitting of 1/T1 values (h) for SZG nanoprobe at different pH levels (5.0 and 7.4) as a function of Gd concentration (mM). (g, i) T2-weighted MR images (g) and the linear fitting of 1/T2 values (i) for SZG nanoprobe at different pH levels (5.0 and 7.4) as a function of Fe concentration (mM).![]()
Figure 3. The dual responsiveness of T1 and T2 MR signals in cells. (a) The cellular uptake of SZG nanoprobe by 4T1 cells was investigated using the fluorescence microscopy. (b, c) Representative T1 (b) and T2 (c) mapping images of SZG incubated with 4T1 and MCF-10A cells at various incubation times (0, 0.5, 1, 2, 4, and 6 h) (n = 3). (d, e) The corresponding R1 (d) and R2 (e) values of SZG nanoprobe incubated with 4T1 and MCF-10A cells for different incubation times (n = 3). (f) 4T1 cell viabilities following treatment with various concentrations of SPIO and SZG. Data are presented as mean ± SD from three independent samples. Data analysis was performed using t-tests to compare two groups. n.s., not significant; *p < 0.05, **p < 0.01, ***p < 0.001.![]()
Figure 4. In vivo MRI evaluation of SZG nanoparticles for mice subcutaneous tumor model. (a, b) T1 and T2 mapping (a), T1-weighted and T2-weighted images (b) of SZG nanoparticle treated tumor-bearing mice at different time points (n = 3). (c, d) Corresponding R1 and R2 values (c), T1 and T2 SNR values (d) of tumor after different treatments (n = 3). (e, f) Representative enhanced images (e) and TNR (f) after different drug injections using DESI processing (n = 3). (g) Prussian blue staining shows iron accumulation from SZG nanoprobes in tumors. Data statistics were analyzed by calculating Two-way ANOVA analysis of variations for multiple groups. n.s., not significant; *p < 0.05, **p < 0.01, ***p < 0.001.Meng Luo, Jiajing Guo, Yi Zhu, Jiali Deng, Hongwei Lu, Lei Li, Zhongling Wang. A rapid-response smart nanoplatform with dual T1-T2 activation for acidic microenvironment imaging. Sci. China Mater. (2024).https://doi.org/10.1007/s40843-024-3103-x
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