Human serum albumin: A nanomedicine platform targeting breast cancer cells

Breast cancer is the second most common and the most life-threatening cancer in women worldwide. Current chemotherapy for cancer treatment has made significant progress; however, strategic drug delivery systems are necessary to enhance therapeutic effects and reduce the side effects. Here, we designed a nanomedicine platform of human serum albumin (HSA) conjugated with two therapeutic drugs, transforming growth factor (TGF)-β1 antibody and methotrexate (MTX), and cancer-targeting folic acid (FOL). EDC/NHS chemistry was used to conjugate MTX and FOL to HSA or HSA to TGF-β1 antibody (TGFAb). In order to enhance the anticancer properties, HSA was optimized by conjugating 8 different concentration ratios of FOL and MTX to HSA (FOL-HSA-MTX). More FOL conjugation to HSA increased the cellular uptake of FOL-HSA-MTX by human MDA-MB-231 breast cancer cells that overexpressed FOL receptors. The highest cellular toxicity of FOL-HSA-MTX to MDA-MB-231 was observed at FOL:MTX (4 mM: 6 mM). MDA-MB-231 has been known to produce more extracellular TGF-β1; however, TGFAb on HSA scavenged extracellular TGF-β1 of cancer cells by 91.1 ± 3.0% resulting in similar extracellular TGF-β1 level to a normal cell, RIN cells (β-cells). Due to their efficacy and tunable properties, we anticipate numerous applications of multifunctional HSA in treating cancers.