Self-Assembly of DNA–Porphyrin Supramolecular Amphiphile into Biocompatible Nanoparticles for Photoacoustic Imaging

Photoacoustic imaging (PAI) holds great promise for biomedical research and possesses several distinctive advantages over other imaging techniques, and it typically explores either endogenous or exogenous PAI contrast agents for image generation. However, most of the deadly diseases do not possess good endogenous PAI contrast agents, and hence it is extremely important to develop potential exogenous contrast agents. Herein, the noncovalent synthesis of DNA–porphyrin amphiphiles and their spontaneous self-assembly into spherical NPs as a potential PAI contrast agent is reported. Our design strategy involves the assembly between a cationic porphyrin derivative and an anionic DNA resulting in the formation of supramolecular amphiphile, wherein the cationic porphyrin is tethered along the anionic DNA backbone via strong electrostatic interaction in a chiral fashion. The subsequent amphiphilicity-driven self-assembly of the supramolecular amphiphile leads to the formation of spherical NPs. The NPs exhibit nearly complete quenching of fluorescence of porphyrin due to its very strong π-stacking of porphyrins in the self-assembled state. The nearly complete quenching of fluorescence leads to the efficient conversion of light energy to heat energy and hence could act as an excellent PAI contrast agent. In addition, remarkable stability of the NPs under physiological conditions, biocompatibility, water solubility, and tunability are promising features for its use as a PAI contrast agent for clinical applications. Another important highlight of our strategy is the less laborious noncovalent synthesis of porphyrin-based PAI contrast agent. Our results demonstrate a unique strategy for the rational design and construction of highly stable and efficient photoacoustic NPs for noninvasive disease detection.