Hyaluronic acid dressing of hydrophobic carbon nanodots: A self-assembling strategy of hybrid nanocomposites with theranostic potential

We propose a rational design of hyaluronic acid-dressed red-emissive carbon dots (CDs), with a well-structured hydrophobic core capable of locally delivering high amount doxorubicin (Doxo) (> 9% w/w) and heat (hyperthermia) in a light stimuli sensitive fashion. We combined in a unique micelle-like superstructure the peculiar optical properties of CDs (NIR photothermal conversion and red fluorescence) with the ability of hyaluronic acid (HA) shell of stabilizing nanomedicines in aqueous environment and recognizing cancer cells overexpressing CD44 receptors on their membranes, thus giving rise to smart theranostic agents useful in cancer imaging and NIR-triggered chemo-phototherapy of solid tumors. Hydrophobic CDs, named HCDs, were used as functional beads to self-assemble amphiphilic HA derivatives carrying polylactic acid side chains (HA-g-PLA), yielding to light-sensitive and biodegradable core-shell superstructures. We explored the biocompatibility and synergistic effects of chemo-phototherapy combination, together with fluorescence imaging, showing the huge potential of the proposed engineering strategy in improving efficacy.