Development of Tunable Rose Bengal-Based nanoGUMBOS as Potential Selective Chemotherapeutic Agents

As cancer remains one of the greatest threats to the global population, the development of chemotherapeutic agents that are selective and tunable is of critical importance. Herein, a series of Rose Bengal (RB)-based GUMBOS, a <i><b>g</b></i> roup of <i><b>u</b></i> niform <i><b>m</b></i> aterials <i><b>b</b></i> ased on <i><b>o</b></i> rganic <i><b>s</b></i> alts, was synthesized via counterion exchange between [Na]₂[RB] and three organic cations: tetrabutylphosphonium bromide [TBP]-[Br], tetraphenylphosphonium chloride [TPP]-[Cl], and 1-dodecyl-3-methylimidazolium chloride [C₁₂MIm]-[Cl]. The resulting GUMBOS were characterized through FT-IR, ESI-MS, NMR, and UV-vis spectroscopy. Partition coefficient studies indicated that all GUMBOS exhibited hydrophobic physicochemical characteristics. These hydrophobic RB-based GUMBOS were formed into nanoparticles via the reprecipitation method and exhibited average diameter sizes below 85 nm with moderately negative ζ-potentials all below -30 mV. Permeability through biological membranes was assessed by an <i>in vitro</i> PAMPA, revealing enhanced passive diffusion at 10 μM solutions. The cytotoxic activity of the nanoparticles was assessed in A549 lung carcinoma cells as well as noncancerous HEK239 human embryonic kidney cells. The A549 cell line exhibited mainly apoptotic characteristics, with a lower average cell viability of 22.6% from treatment with [C₁₂MIm]₂[RB] nanoGUMBOS. Moreover, the HEK239 cells exhibited a higher viability of 47.1% with the same treatment. The IC50 of the [C₁₂MIm]₂[RB] nanoGUMBOS treatment on cancerous cells was 2.16 μM, with a selectivity index of 2.1. These findings demonstrate the novelty of RB-based nanoGUMBOS as tunable and selective chemotherapeutic agents.