Anti-Canine Mammary Carcinoma Effects of mPP-Based Nano-Micelles Encapsulating DPIA.

Triple negative breast cancer (TNBC) presents a significant challenge in breast cancer treatment. Canine mammary carcinoma, characterized by spontaneous tumours in female dogs, serves as a robust spontaneous model for TNBC. In this study, DPIA, a potent antitumor agent, was encapsulated into synthesized mPEG-PCL (mPP) to form nano-micelles, aiming to enhance its in vivo therapeutic efficacy. DPIA@mPP exhibited more uniform dispersion and a spheroid-like architecture, with a drug loading rate of 4.31% and an encapsulation rate of 13.10%. Both DPIA@mPP and free DPIA exhibited comparable and significant cytotoxicity against canine mammary carcinoma cells (CMT-7364) in vitro. Encapsulation into mPP enhanced DPIA uptake by CMT-7364 cells, increasing tumour inhibition from 30.31% to 48.55%, while markedly reducing in vivo toxicity. Overall, the DPIA@mPP group demonstrated superior in vivo antitumor efficacy and a good safety profile. Furthermore, preliminary mechanistic studies suggest that DPIA@mPP may promote apoptosis in CMT-7364 cells, potentially through the inhibition of the PI3K/AKT signalling pathway, offering novel insights into TNBC treatment strategies.