Engineered polymer micelles with tunable gas release for effective reduction of local fat deposits.

Demand is rising for non-surgical, site-specific fat reduction. This study presents fully organic biodegradable polymer micelles capable of intrinsic carbon dioxide (CO2) gas generation for adipocytolysis. Amphiphilic methoxy-poly(ethylene glycol) (mPEG) derivatives containing tri-carbonate groups (mPEG-T-OC) are synthesized to enhance CO2 release. These amphiphilic polymers form micellar structures and exhibit sustained CO2 release profiles under physiological conditions. To improve adipose tissue uptake, micelles are functionalized with nona‑arginine (r9), a cell-penetrating peptide that promotes macropinocytosis (r9‑PEG‑T‑OC micelles). Hydrolytic CO2 released from micelles disrupts plasma membranes and induces necrosis of adipocytes and adipose‑derived stem cells in vitro. In obese mice, subcutaneous injection of r9‑PEG‑T‑OC micelles achieves significant local fat pad reduction without systemic toxicity, with prolonged retention in adipose tissue and reduced off-target accumulation. This gas‑generating platform functions without additional drugs or inorganic compounds, offering an innovative strategy for localized adipose tissue reduction and demonstrating the therapeutic potential of polymer-based intracellular gas delivery systems.