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Purpose Gene therapy is a promising and novel therapeutic strategy for many mutated gene-associated diseases, including breast cancer. However, it poses significant biological drawbacks such as rapid clearance from the circulatory system and low cellular uptake of the exogenously delivered functional nucleic acids. The development of efficient and biocompatible carriers for genetic materials has been extensively explored in the literature, and the functionalization of nanoparticles (NPs) with cancer cell-recognizing ligands has become an attractive approach to promote tumor targetability and efficient cellular internalization via endocytosis. Methods This study introduced self-assembling targeting ligands, including transferrin and fibronectin with the ability to electrostatically interact with strontium nanoparticles (SNPs), and then analyzed their influence on size and zeta potential of the resultant hybrid SNPs, cellular uptake and expression efficiency of transgene-loaded hybrid NPs. Results Smaller ligand-coated SNPs (LCSNPs) remarkably increased gene transfection activity in both MCF-7 and 4T1 cells as well as nucleic acid localization into tumor tissues with improved tumor regression activity in a 4T1-tumor xenograft mouse model. Conclusion LCSNPs-mediated delivery of p53 gene and MAPK siRNA provided a proof-of-concept for the functionalized nanocarrier formulation in order to inhibit breast cancer cell growth.

Active targeting via ligand-anchored pH-responsive strontium nanoparticles for efficient nucleic acid delivery into breast cancer cells