A pH-responsive nanoparticle targets the neurokinin 1 receptor in endosomes to prevent chronic pain.

ABSTRACT: Nanoparticle-mediated drug delivery is especially useful for targets within endosomes because of the endosomal transport mechanisms of many nanomedicines within cells. Here, we report the design of a pH-responsive, soft polymeric nanoparticle for the targeting of acidified endosomes to precisely inhibit endosomal signalling events leading to chronic pain. In chronic pain, the substance P (SP) neurokinin 1 receptor (NK₁R) redistributes from the plasma membrane to acidified endosomes, where it signals to maintain pain. Therefore, the NK₁R in endosomes provides an important target for pain relief. The pH-responsive nanoparticles enter cells by clathrin- and dynamin-dependent endocytosis and accumulate in NK₁R-containing endosomes. Following intrathecal injecti

SUBMITTER: Ramirez-Garcia PD 

PROVIDER: S-EPMC7765343 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature