NanoTLZ prolonged the overall survival and was more effective in inducing tumor regression compared to free Talazoparib in BRCA-deficient mice. Brca1Co/Co;MMTV-Cre;p53+/- mice were started on treatment when tumors were 4 mm in diameter. The treatments were either control (saline, i.v.), empty nanoparticles (vehicle, i.v.), NanoTLZ (i.v., 0.33 mg/kg), free Talazoparib (i.v.TLZ, i.v., 0.33 mg/kg), or free Talazoparib (oral TLZ, gavage, 0.33 mg/kg). Treatment was given three times a week. Mice were sacrificed when the tumor reached 10 mm in diameter. A. Growth curves of individual tumors treated with saline or NanoTLZ. (N= 6 in saline and 9 in NanoTLZ groups) B. NanoTLZ significantly prolonged the overall survival of BRCA-deficient mice compared to controls, oral TLZ and i.v. TLZ. N=5 in saline and vehicle groups, N=8 in NanoTLZ and TLZ treatment groups. Symbols in red: *, p<0.05, **, p<0.0.1, ***, p<0.001 vs. NanoTLZ. Symbols in black: ***, p<0.001 vs. saline. C. NanoTLZ significantly improved the progression free survival of BRCA-deficient mice compared to i.v. TLZ and oral TLZ. N=8. **, p<0.0.1, ***, p<0.001 vs. NanoTLZ. D. All tumors were classified into three groups: regressing (tumor volume decreased more than 50%), no change (tumor volume did not increase or decrease by more than 50%), active growth (tumor continued to grow and tumor volume increased more than 50%). N=6-19/group. *, p<0.05. vs. saline; #, p<0.05 vs. NanoTLZ.