Delivery of bortezomib with nanoparticles for basal-like triple-negative breast cancer therapy

Abstract

Basal-like triple negative breast cancer (TNBC) has received particular clinical interest due to its high frequency, poor baseline prognosis and lack of effective clinical therapy. Bortezomib, which was the first proteasome inhibitor approved for the treatment of multiple myeloma, has been proven to be worth investigating for this subtype of breast cancer. In our study, the amphiphilic copolymer poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-b-PLA) was utilized as an excellent delivery carrier of bortezomib (BTZ) to overcome its clinical limitations including low water solubility and unstable properties. Bortezomib encapsulated nanoparticles (NPBTZ) can efficiently deliver the drug into both CSCs (cancer stem cells) and non-CSCs, resulting in proliferation inhibition and apoptosis induction. Remarkably, NPBTZ can more effectively affect the stemness of CSCs compared with free BTZ. Administration of this drug delivery system can markedly prolong the bortezomib circulation half-life and augment the enrichment of drugs in tumor tissue, then enhance the suppression of tumor growth, suggesting the therapeutic promise of NPBTZ delivery in basal-like TNBC therapy.

Keywords: Basal-like triple negative breast cancer; Bortezomib; Cancer stem cells; Nanoparticle; Poly(ethylene glycol)-block-poly(d,l-lactide).