Molecular bottlebrush as a unimolecular vehicle with tunable shape for photothermal cancer therapy

Abstract Morphology of delivery nanovehicle plays a significant role in bioavailability of drug. Molecular bottlebrush (MBB)-based unimolecular micelle, with tunable morphologies including sphere, rod, and worm, offers a new aspect to uncover the relationship between morphology and bio-behaviors. In this study, a series of MBB as unimolecular micelle with core-shell structures were tailor-made through controlled/living polymerization and click chemistry, and served as carriers of IR780 photothermal agent. With an excellent IR780 loading content of up to ca . 25%, these molecular nanovehicles still maintained their molecular morphologies and did not aggregate in cell culture medium. Among three MBB, the rodlike one exhibited best performance in cell uptake in the 2D and also in spheroid penetration in 3D cell culture. Furthermore, this rodlike system had preferential accumulation in tumor in vivo and excellent effect on photothermal cancer therapy which effectively inhibited tumor growth. These results demonstrated an important role of nanoparticle shape on bio-behaviors and the unimolecular micelle could be a promising nanovehicle with precisely defined structure for biomedicine applications.