Precision Strike at Lipid Droplets by Spherical Nano-Browning Agents Promotes Obesity Remission

Obesity is a major global public health challenge, driving the development of numerous metabolic disorders and associated comorbidities such as type 2 diabetes, cardiovascular disease, and cancer. The "browning" agents function similarly to physical exercise to transform white adipocytes into brown-like adipocytes for accelerating metabolism and combating obesity. It is challenging to enhance the bioavailability of natural browning agents (e.g., capsaicin) while enabling distribution tracing for personalized dose control. Here, browning functional groups are grafted around a lipid droplet-navigation core to solve this problem. The "tennis ball" structure formed by the two precursors termed anti-obesity bifunctional carbon dots (AB-CDs) synergize to selectively target, illuminate, and break down lipid droplets (LDs). The carbonization of parent precursors serves as a nanodrug and enables label-free tracking of drug metabolism for personalized dose control during weight management. AB-CDs therapy on high-fat-diet-induced obese mice surpassed browning molecules in weight loss, systemic inflammation reduction, reversal of metabolic disorders, fatty liver, and fatty airways. The ultrasmall AB-CDs nanodrug integrates targeted obesity medication with self-reporting traceability. This lesion-positioning nanodrug strategy seeks optimal balance between drug molecule bioavailability and metabolic tracking in chronic disease managements.