Journal
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 15, Issue 2, Pages 373-381Publisher
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2019.2693
Keywords
Polymeric Micelle; Redox-Responsive; Endosome Escape; Intracellular Drug Delivery; Boron Neutron Capture Therapy
Funding
- National Key R&D Program of China [2017YFA0207900]
- National Young 1000 Talents Plan [D1424002A]
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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 B-10-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 B-10-compounds for efficient tumor BNCT. However, current clinical approved B-10-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.
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