The efficacy of enzyme replacement therapy (ERT) for lysosomal storage diseases (LSDs) possibly depends on the cellular uptake of recombinant lysosomal enzymes (LEs), and it is known that cation-independent mannose 6-phosphate receptor (CI-M6PR) on the cell membrane is predominantly involved in the endocytosis of many LEs. To examine the biomolecular interaction between therapeutic LEs and CI-M6PR, we biophysically analyzed the complex formation of four LEs available with domain 9 of human CI-M6PR, a binding site of the receptor, by means of surface plasmon resonance (SPR) biosensor assays. The results revealed that the affinity of the LEs for domain 9 of the receptor increased in the following order: laronidase, agalsidase beta, idursulfase, and alglucosidase alfa; and the high affinity of laronidase for domain 9 of CI-M6PR was due to fast complex formation rather than slow dissociation of the complex. The affinity of the enzymes for domain 9 of CI-M6PR almost coincided with their cellular uptake. The SPR biosensor assay is sensitive and provides important information for the development of effective therapeutic LEs for LSDs.

溶酶体贮积病（LSDs）的酶替代疗法（ERT）的功效可能取决于重组溶酶体酶（LEs）的细胞吸收，并且已知阳离子上不依赖于阳离子的甘露糖6-磷酸受体（CI-M6PR）细胞膜主要参与许多LE的胞吞作用。为了检查治疗性LE与CI-M6PR之间的生物分子相互作用，我们通过表面等离振子共振（SPR）生物传感器分析，通过生物学方法分析了四个LE与人CI-M6PR的结构域9（受体的结合位点）的复杂形成。 。结果表明，LE对受体的结构域9的亲和力以下列顺序增加：拉罗尼德酶，阿加糖苷酶β，艾杜糖苷酶和阿糖苷酶α。Laronidase对CI-M6PR结构域9的高亲和力是由于复合物的快速形成而不是复合物的缓慢解离。酶对CI-M6PR结构域9的亲和力几乎与其细胞摄取一致。SPR生物传感器测定灵敏，可为开发LSD的有效治疗性LE提供重要信息。