Zhang Weiqi, Tung Ching-Hsuan
Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, 413 East 69th Street, Box 290, New York, NY, 10021, USA.
Chemistry. 2018 Feb 9;24(9):2089-2093. doi: 10.1002/chem.201705697. Epub 2018 Jan 16.
Breaking the lysosome helps its sequestered payloads access their molecular targets in cells and thus enhances the intracellular drug delivery. Current strategies for lysosomal escape involve direct physical interactions with the lipid membrane. These interactions pose a systemic toxicity and uncontrolled membrane rupture risk. Here, we report a light-detonated lysosome disruption using a hyaluronan (HA) nanogel packed with toludine blue (TB). The HA/TB nanogel is concentrated within the lysosomes. The applied light assists TB in generating reactive oxygen species and destroying the lysosome in situ, both in cells and isolated lysosomes. Real time fluorescent tracking reveals that quenched TB fluorescence recovers along with lysosome explosion, relocates to the nucleus, and is presented as a fluorescent sparkling in cells. This HA/TB, composed of all clinically approved materials, represents a biocompatible and facile strategy to "bomb" lysosomes in a spatiotemporally controlled fashion.
破坏溶酶体有助于其隔离的有效载荷作用于细胞内的分子靶点，从而增强细胞内药物递送。目前的溶酶体逃逸策略涉及与脂质膜的直接物理相互作用。这些相互作用存在全身毒性和不受控制的膜破裂风险。在此，我们报告了一种使用填充甲苯胺蓝（TB）的透明质酸（HA）纳米凝胶进行光引爆的溶酶体破坏方法。HA/TB纳米凝胶在溶酶体内聚集。施加的光协助TB产生活性氧并在细胞和分离的溶酶体中原位破坏溶酶体。实时荧光追踪显示，淬灭的TB荧光随着溶酶体爆炸而恢复，重新定位到细胞核，并在细胞中呈现为荧光闪烁。这种由所有临床批准材料组成的HA/TB代表了一种生物相容性好且简便的策略，可在时空可控的方式下“轰炸”溶酶体。
