Lysosomal membrane permeabilization (LMP) engaged in multiple human diseases is accompanied by relocation of cytosolic galectin into LMP⁺ lysosomes. We herein reported a galectin trafficking-targeted method to image LMP using two kinds of glyco-dendrimers, a sialic acid-terminated dendrimer labeled with pH-inert rhodamine and a lactose-terminated dendrimer labeled with fluorescein that becomes green-emissive in pH-elevated lysosomes. Albeit both accumulated in physiological lysosomes, the former is released from LMP⁺ lysosomes while the latter binds to galectin accumulated in LMP⁺ lysosomes and thus trapped in LMP⁺ lysosomes. Accordingly, LMP⁺ lysosomes exhibit loss of red fluorescence and turn-on green fluorescence due to loss of lysosomal acidity. This red-to-green color switch enables discernment of LMP⁺ lysosomes from physiological lysosomes and pH-elevated lysosomes and can be further utilized to detect LMP in distinct cell death pathways. These results suggest the utility of galectin trafficking pathway-integrated synthetic probes for detection of LMP, a key factor for diseased cells.

中文翻译：

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半乳糖凝集素运输途径启用的溶酶体膜透化的颜色可切换检测

参与多种人类疾病的溶酶体膜透化 (LMP) 伴随着细胞溶质半乳糖凝集素重新定位到 LMP ⁺溶酶体中。我们在此报告了一种半乳糖凝集素运输靶向方法，使用两种糖树枝状大分子对 LMP 进行成像，一种用 pH 惰性罗丹明标记的唾液酸末端树枝状大分子和一种用荧光素标记的乳糖末端树枝状大分子，荧光素在 pH 升高时会发出绿光。溶酶体。尽管两者都在生理溶酶体中积累，但前者从 LMP ⁺溶酶体中释放出来，而后者与在 LMP ⁺溶酶体中积累的半乳糖凝集素结合，从而被困在 LMP ⁺溶酶体中。因此，LMP ⁺由于溶酶体酸度的丧失，溶酶体表现出红色荧光的丧失和绿色荧光的开启。这种从红到绿的颜色切换可以从生理溶酶体和 pH 升高的溶酶体中区分LMP ⁺溶酶体，并可进一步用于检测不同细胞死亡途径中的 LMP。这些结果表明半乳糖凝集素运输途径集成的合成探针可用于检测 LMP，这是患病细胞的关键因素。