Hyaluronan functionalized pH-responsive calcium carbonate nanoparticles for local treatment of breast cancer

Abstract

[Excerpt] Introduction: Current radio- and chemotherapies are not efficient and many tumors remain resistant to conventional cancer treatments. Specific properties and signaling molecules from tumor microenvironment (TME) have been explored to increase treatment efficacy. An example is the acidic pH of the TME that has been explored to develop stimuli responsive release systems. Herein, we obtained biocompatible calcium carbonate (CaCO3) nanoparticles that are stable at neutral pH but dissolve at acidic conditions and evaluated their potential as a drug carrier for local cancer treatment. METHODS: CaCO3 nanoparticles were produced by co-precipitation of calcium chloride (CaCl2) and sodium carbonate (Na2CO3) in the presence of ethylene glycol [1]. Rhodamine was encapsulated as a model drug. The morphology and diameter of the nanoparticles were determined by scanning electron microscopy and dynamic laser scattering. The particles were coated by layer-by-layer (LbL) assembly of poly-L-lysine and hyaluronic acid (HA). The release was studied in phosphate buffered saline at pH 6.3 and 7.4. Cultures of two breast cancer cell lines (MDA-MB-231 and SK-BR-3) and a healthy epithelial cell line MCF10A (control) were observed under confocal laser scanning microscopy to assess particles internalization and their effect on cell viability (live/dead staining) and metabolic activity (Alamar Blue). [...]