Materials Today Advances (Aug 2023)
CO2-Responsive drug delivery system created by supramolecular design and assembly for safer, more effective cancer therapy
Abstract
We developed a carbon dioxide (CO2)-responsive supramolecular drug carrier system through a combination of hydrophobic CO2-sensitive imidazole-containing rhodamine 6G (I–R6G) as an efficient anticancer agent and hydrophilic ureido-cytosine (UrCy) end-capped polyethylene glycol (UrCy-PEG) as a self-assembled nanocarrier that could potentially enhance the safety and efficiency of cancer treatment. Owing to the self-complementary quadruple hydrogen bonding interactions between the UrCy moieties at the polymer chain ends, UrCy-PEG can spontaneously self-assemble into spherical-like nanoobjects in water that can effectively encapsulate hydrophobic I–R6G and form co-assembled nanoparticles with tunable sizes (depending on the I–R6G loading content). These nanoparticles display several notable physical features, including high structural stability in normal physiological aqueous media or red blood cell-containing media, unique CO2-responsiveness, and controlled CO2-sensitive I–R6G release. In vitro cytotoxicity assays clearly indicated I–R6G-loaded nanoparticles exerted selective cytotoxicity towards cancer cells, but had no adverse effects on normal cells. I–R6G-loaded nanoparticles exerted significantly higher levels of cytotoxicity at lower doses in CO2-treated cell culture media compared to I–R6G-loaded nanoparticles in pristine media. More importantly, cellular assays demonstrated that—in comparison to I–R6G-loaded nanoparticles in pristine media—CO2-treated culture media accelerated macropinocytic internalization of I–R6G-loaded nanoparticles into cancer cells, and subsequently led to more rapid induction of apoptosis in cancer cells and massive programmed cell death. Thus, this newly created system may act as a potential route to manipulate the drug delivery and release performance of self-assembled nanobjects for efficient cancer therapy.
