Lipase-triggered drug release from BCL2 inhibitor ABT-199-loaded nanoparticles to elevate anti-leukemic activity through enhanced drug targeting on the mitochondrial membrane.

Selective BCL2 inhibitor ABT-199 has been approved to treat hematological malignancies including acute myeloid leukemia (AML). However, acquired drug resistance and severe side effects occur after extended treatment limiting the clinical usage of ABT-199. Here, we successfully encapsulated pure ABT-199 in amphiphilic mPEG-b-PTMC block copolymer, forming mPEG-b-PTMC@ABT-199 nanoparticles (abbreviated as PEG-ABT-199), which presented better aqueous dispersion and higher efficiency of loading and encapsulation than pure ABT-199.