Delivery of miR-139–5p from responsive human serum albumin nanoparticles boosts doxorubicin biological effects on triple negative breast cancer cells

Cystamine-derivatized Human Serum Albumin (HSAcys) was tested as a redox-responsive cationic specimen for microRNA (miRNA) vectorization to triple-negative breast cancer (TNBC) cells. MiR-139-5p was used as gene material, since it is significantly down-regulated in TNBC, thus suggesting its re-introduction as a promising therapeutic approach. The complexation of HSAcys with miR-139-5p allowed the development of a nanoparticle system (miR-139-5p mRH-NPs) with a mean diameter of 170 ± 7.0 nm with a polydispersity index of 0.18. miR-139-5p mRH-NPs exhibited effectiveness in both protecting miR-139-5p from RNAse activity, delivery and enhancing its release in cancer cells. Moreover, the restoration of miR-139-5p by its re-introduction through miR-139-5p mRH-NPs is functionally active in cellular models of TNBC (MDA-MB-231 and HCC-1395) reducing their clonogenic ability, increasing their sensitivity to the chemotherapeutic agent Doxorubicin (Dox) and impairing their migratory ability. Thus, this study contributes in addressing the critical challenges of miRNA-based therapy and proposes HSAcys nanoparticle-mediated delivery of miRNAs as a potential adjuvant strategy to enhance therapeutic efficacy in cancer treatment.