Enhanced intracellular delivery of small molecules and drugs via non-covalent ternary dispersions of single-wall carbon nanotubes.

Abstract

Albumins are used biologically and pharmacologically as transport proteins to deliver molecules to cells. Albumins also efficiently coat single-wall carbon nanotubes (SWCNTs) and promote their entry into mammalian and immune cells by the millions. Here, we show SWCNTs dispersed with bovine serum albumin (BSA) that are pre-loaded with rhodamine B (RB), small hydrophobic dye molecules that we consider here as models for drugs, drastically increase delivery of RB to HeLa cells and macrophages in culture. We determine spatial and concentration distribution of RB by independently visualizing SWCNTs and RB within the cells using unique SWCNT NIR fluorescence and fluorescence lifetime imaging of RB. The SWCNTs-BSA-RB ternary complexes are stable in water for days, and RB is only released when BSA is thermally or enzymatically denatured. We demonstrate efficacy of this approach by delivering daunomycin, a fluorescent chemotherapeutic drug that reduces proliferation in HeLa cells. Furthermore, we use molecular dynamics simulations to identify separate regions in BSA for drug loading and binding to SWCNTs. Together, our results demonstrate a pathway to enhance the delivery of a wide variety of drugs to cells through SWCNTs coated with albumin pre-loaded with drug molecules.