Polymeric Micelles with Endosome Escape and Redox-Responsive Functions for Enhanced Intracellular Drug Delivery

Efficient intracellular delivery of bioactive compounds into cancer cells is critically important for treatment, as some compounds only validate for therapy after entering cancer cells. The boron neutron capture therapy (BNCT) applies thermal neutron irradiation to react with ¹⁰B-compounds that existed inside cancer cells to generate secondary killing irradiations to eradicate cancer cells. The effective distance of the emitted secondary killing irradiations is as long as a cellular diameter, which requires the cellular uptake of ¹⁰B-compounds for efficient tumor BNCT. However, current clinical approved ¹⁰B-compound of sodium borocaptate (BSH) exhibits low cellular uptake by cancer cells, which limits the therapeutic efficacy. Herein, the multifunctional polymeric micelles with endosome escape and redox-responsive functions have been developed by self-assembly from the BSH-conjugated block copolymers for enhanced delivery of BSH into cancer cells. The BSH-loaded polymeric micelles (BSH/micelle) showed a hydrodynamic diameter around 50 nm, and the size distribution was monodisperse. The BSH/micelle were stable in normal physiological environment, while the BSH could be released in responding to high level of redox-potential in cancer cells. Besides, intracellular delivery of BSH was highly promoted by BSH/micelle through the endosome escape function of micelles, which further increased the tumor therapeutic efficacy by BNCT.