Figure 5.

Improved combinatorial therapy in vivo with coloaded drug PNPs. (A,B) Athymic, nude male mice with human prostate cancer xenografts of the androgen-receptor-positive cell line LNCaP were treated with PNPs carrying both the PI3K inhibitor BEZ235 and the androgen receptor antagonist MDV3100 (enzalutamide, Xtandi) to simultaneously inhibit these pathways’ crosstalk. During the course of a week, and four iv administrations (blue triangles), the PNPs achieved tumor regression, as opposed to the free drugs (B/M = BEZ235/MDV3100; n per cohort = 3). (C,D) Improved survival and tumor regression after treatment of athymic, nude female mice that had xenografts of the human breast cancer cell line MDA-MB-468 with PNPs coloaded with doxorubicin and the MEK inhibitor AZD6244 (Selumetinib). The animals were treated every other day during the course of 40 days, through iv administration of the agents (D/A = Doxorubicin/AZD6244; n per cohort = 3). Fluorescence-based imaging of naïve, untreated animals showed accumulation of drug-free DiR-loaded PNPs at the tumor 24 h post iv administration (inset). Means ± SEM.