Sub-10 nm Theranostic Unimolecular Micelles with High Tumor-Specific Accumulation, Retention and Inhibitory Effect

Theranostic agents that integrate far-red/near-infrared fluorescence and anticancer drugs are useful for biomedical applications such as imaging-guided therapy of cancers. However, the clinical translation of previously reported theranostic agents is still limited by factors such as weak fluorescence of the imaging probe, premature and off-target release of fluorophores and drugs during blood circulation, the long-term retention in the reticuloendothelial system, and side effects of toxicity. Here, we report a new type of ultrasmall theranostic unimolecular micelles with an average diameter below 10 nm, and dual functionalities of bright fluorescence in the spectral window of 600-800 nm toward noninvasive in vivo bioimaging and covalently-bound anticancer drugs for specific cancer treatment. Each unimolecular micelle is formed by an amphiphilic bottlebrush copolymer containing a fluorescent conjugated backbone of poly(fluorene-alt-(4,7-bis(hexylthien)-2,1,3-benzothiadiazole)), from which hydrophobic disul...