Gao Lei, Han Shoufa
Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, and The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen 361005, China.
Anal Chem. 2021 Sep 21;93(37):12639-12647. doi: 10.1021/acs.analchem.1c02387. Epub 2021 Sep 7.
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.
参与多种人类疾病的溶酶体膜通透性（LMP）伴随着胞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靶向半乳糖凝集素转运的方法，使用两种糖树状大分子对LMP进行成像，一种是用pH惰性罗丹明标记的唾液酸末端树状大分子，另一种是用荧光素标记的乳糖末端树状大分子，其在pH升高的溶酶体中发出绿色荧光。尽管两者都在生理性溶酶体中积累，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，因此被困在LMP溶酶体中。因此，由于溶酶体酸度的丧失，LMP溶酶体呈现红色荧光的丧失和绿色荧光的开启。这种红到绿的颜色转换能够区分LMP溶酶体与生理性溶酶体和pH升高的溶酶体，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，整合半乳糖凝集素转运途径的合成探针可用于检测LMP，这是患病细胞的关键因素。
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