Carbon Nanodots Modified with Catechol-Borane Moieties for pH-Stimulated Doxorubicin Delivery: Toward Nuclear Targeting

An ultrafine fluorescent nanocarrier (<5 nm) inspired by catechol boronate interaction is developed to escort doxorubicin (DOX) directly to nuclei for site-specific drug delivery. In this study, biocompatible carbon dot is postmodified with catechol and boronic acid to initiate catechol boronate complexation and form an ultrafine-sized nanocarrier. Served as a drug delivery vehicle (DDV), the resultant nanocarrier can load DOX through noninvasive adsorption with a capacity as high as 84.28% (w/w), which is reported here for the first time. Moreover, due to the dynamic reversibility of the catechol boronate interaction, the boronic acid could be exposed under the acidity inside tumor cells, which will assist the nanocarrier to bind against glucosamine presented at nucleoporin 62 (NUP62). The DDV is thus capable of selective presentation of its bioactivity so as to enter through the nuclear pore complex (NPC) channel via NUP62 and release DOX inside nuclei directly. In addition, the intrinsic green fluorescence from the DDV not only makes the nanocarrier trackable for cell imaging but also confirms its selective binding to NPC as it accumulates dominantly in the nuclear membrane and enters into the nuclei. Considering the tumor cell specificity, stimuli responsiveness, and NUP62 targeting, the ultrafine fluorescent nanocarrier here holds great promise in nuclear targeted chemotherapy.