Very recent red-emissive
carbon nanodots (CDs) have shown potential as near-infrared converting tools to produce local heat useful in
cancer theranostics. Besides, CDs seem very appealing for clinical applications combining
hyperthermia, imaging, and drug delivery in a single platform capable of selectively targeting
cancer cells. However, CDs still suffer from dramatic dot-to-dot variability issues such that a rational design of their structural, optical, and chemical characteristics for medical applications has been impossible so far. Herein, we report for the first time a simple and highly controllable layer-by-layer synthesis of
biotin-decorated CDs with monodisperse size distribution, well established polymeric shell thickness, and degree of surface functionalization, endowed with strong red luminescence and the ability to convert NIR light into heat. These CDs, henceforth named CDs-PEG-BT, consist of a carbonaceous core passivated with
biotin-terminated
PEG2000 chains, which we demonstrate as active targeting groups to recognize
cancer cells. The CDs-PEG-BT are designed to efficiently incorporate a high amount of anticancer drugs such as
irinotecan (16-28%) and to act as NIR-activated nanoheaters capable of triggering
local hyperthermia and massive drug release inside
tumors, thus provoking sudden and efficient
tumor death. The potential of the
irinotecan-loaded CDs-PEG-BT (CDs-PEG-BT@IT) in fluorescence imaging was studied on 2D cultures and on complex 3D spheroids mimicking in vivo
tumor architectures, showing their capability of selectively entering
cancer cells through
biotin receptors overexpressed in cell membranes. The efficient anticancer effect of these CDs was thoroughly assessed on multicellular 3D spheroids and patient organoids (
tumor-on-a-dish preclinical models) to predict the drug response in humans in view of
personalized medicine applications. CDs-PEG-BT@IT have a smart combination of properties, which pave the way to their real-world use as anticancer
theranostic agents for image-guided photothermal applications.