Na⁺/K⁺ ATPase-targeted delivery to metastatic breast cancer models

In this study, we reported doxorubicin (DOX)-encapsulated nanoparticles (NPs) formulated with biocompatible and biodegradable poly (lactic-co-glycolic acid) (PLGA) and modified with a 13-amino acid peptide (S3) against sodium/potassium (Na⁺/K⁺)-ATPase pump alpha subunit to investigate its potential as antitumor agent. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using scanning electron microscope (SEM) and dynamic light scattering (DLS). The encapsulation efficiency and in vitro release during 7 days were evaluated. Comparative in vitro cytotoxicity experiments demonstrated that the S3-conjugated nanoparticles (S3-PLGA-DOX NPs) had higher antiproliferative activity. Flow cytometry analysis confirmed the enhanced cellular uptake of S3-PLGA-DOX NPs in comparison with PLGA-DOX. In vivo study in 4T1 tumor-bearing BALB/C mice revealed that the S3-functionalized DOX-loaded NPs improved antitumor activity and survival rate of 4T1 tumor bearing mice. In this regard, conjugation of S3 peptide to the surface of DOX-loaded PLGA NPs provides site-specific delivery of DOX, inhibits 4T1 tumor growth in vivo and significantly decreases systemic toxicity. The obtained results suggested that the new (Na⁺/K⁺)-ATPase pump-targeted PLGA NPs as a target-selective delivery system for DOX has great potential for the treatment of breast cancer.