Rotaxane dendrimers with hyperbranched macromolecular interlocked structures and size modulation capacity demonstrate drug binding and release ability upon external stimuli. Mass spectrometry imaging (MSI) can offer the high-throughput screening of endogenous/exogenous compounds. Herein, we reported a novel method to display the in situ spatial distribution of label-free monodispersed type III rotaxane dendrimers (RDs) G1 (first generation, size ∼1.5 nm) and G2 (second generation, size ∼5 nm) that were explored as potential drug vehicles in spleen tissue by using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-MSI). Experimental results indicated that the trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile (DCTB) matrix exhibited the best performance for monodispersed type III RDs G1 and G2. The optimized method was successfully applied to map the in vivo spatial distribution of type III RDs G1 and G2 in the spleen from intraperitoneally injected mice. The MALDI-MSI images revealed that RDs G1 and G2 were relatively stable in the spleen within 24 h after administration. It was found that the identified type III RDs G1 and G2 penetrated through the tunica serosa and were predominantly localized in red pulp regions of spleens. They were also mapped in a marginal zone of spleens simultaneously. There was almost no toxicity of type III RDs G1 and G2 to mice spleens from the H&E results. Furthermore, the type III RDs did not induce the expression of inflammatory cytokines from peripheral blood mononuclear cells (PBMCs) or THP-1 monocytes. The MSI analysis not only demonstrated its ability to image select rotaxane dendrimers in a rapid and efficient manner but also provided tremendous assistance on the applications of the further treatment of cancerous tissue as safe drug carriers. Furthermore, the new strategy demonstrated in this study could be applied on other label-free mechanically interlocked molecules, molecular machines, and macromolecules, which opened a new path to evaluate the toxicological and pharmacokinetic characteristics of these novel materials at the suborgan level.

中文翻译：

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非炎症性 III 型轮烷树枝状聚合物的 MALDI-MS 成像分析。

具有超支化大分子互锁结构和尺寸调节能力的轮烷树枝状大分子在外部刺激下表现出药物结合和释放能力。质谱成像 (MSI) 可以提供内源性/外源性化合物的高通量筛选。在此，我们报告了一种新方法来显示已探索的无标记单分散 III 型轮烷树枝状大分子 (RD) G1（第一代，尺寸约 1.5 nm）和 G2（第二代，尺寸约 5 nm）的原位空间分布通过使用基质辅助激光解吸/电离成像质谱（MALDI-MSI）作为脾组织中的潜在药物载体。实验结果表明，反式-2-[3-(4-叔丁基苯基)-2-甲基-2-亚丙烯基]丙二腈 (DCTB) 基质对单分散的 III 型 RD G1 和 G2 表现出最佳性能。优化的方法成功应用于绘制腹腔注射小鼠脾脏中 III 型 RD G1 和 G2 的体内空间分布。MALDI-MSI 图像显示，RDs G1 和 G2 在给药后 24 小时内在脾脏中相对稳定。发现已鉴定的 III 型 RD G1 和 G2 穿透浆膜，主要位于脾脏的红髓区域。它们还同时被定位在脾脏的边缘区域。从 H&E 结果来看，III 型 RDs G1 和 G2 对小鼠脾脏几乎没有毒性。此外，III 型 RD 不会诱导外周血单核细胞 (PBMC) 或 THP-1 单核细胞的炎性细胞因子的表达。MSI分析不仅证明了其能够以快速有效的方式对选择的轮烷树枝状大分子进行成像，而且还为进一步治疗癌组织作为安全药物载体的应用提供了巨大的帮助。此外，本研究中展示的新策略可应用于其他无标记的机械互锁分子、分子机器和大分子，为在亚器官水平评估这些新材料的毒理学和药代动力学特性开辟了新途径。