Synergistic Anticancer Response via Docetaxel- and Oleanolic Acid-Loaded Albumin/Poly(lactide) Nanoparticles in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer with a poor prognosis. A highly effective chemotherapeutic treatment strategy is yet to be developed that would kill cancer cells effectively and delay drug resistance. Combination therapy has emerged as a promising treatment strategy. Here, a human serum albumin/poly(d,l)-lactide core-shell nanoparticle system stabilized by a human serum albumin-oleanolic acid (HSA-OA) conjugate and loaded with docetaxel (DTX) and OA was developed. A thorough physicochemical characterization ensured efficient entrapment of DTX and OA. The synergistic inhibitory effect of DTX and OA via the developed nanoparticle (NP) system was investigated by using combination index analysis on human and murine TNBC, MDA-MB-231, and 4T1 cell lines. The uptake study, cell cycle analysis, apoptosis assay, DNA fragmentation study, reactive oxygen species generation, nuclear staining, and mitochondrial membrane potential assay indicated that the DTX/OA@HOP NPs provided the best inhibition and apoptotic effects when compared with free DTX, free OA, DTX@HOP NPs, and OA@HOP NPs. The in vivo study performed using 4T1-Luc tumor-bearing mice revealed that the DTX/OA@HOP NPs showed maximum tumor growth inhibition with a marked elevation in the apoptotic marker and decreased antiproliferative marker. Thus, the prepared DTX/OA@HOP NPs pose a promising combination therapy for the treatment of TNBC.

Automated summary

In this study, a nanoparticle-based combination therapy was developed to inhibit the growth of triple-negative breast cancer cells and induce apoptosis through the synergistic effect of the two drugs. The nanoparticle system exhibited better therapeutic effects compared to the free drugs. In vivo experiments showed that the nanoparticles effectively inhibited tumor growth and induced apoptosis.