Sterically chained amino acid-rich water-soluble carbon quantum dots as a robust tumor-targeted drug delivery platform

Effective antitumor nanomedicines maximize therapeutic efficacy by prolonging drug circulation time and transporting drugs to target sites. Although numerous nanocarriers have been developed for accurate tumor targeting, their limited water solubility makes their stable storage challenging, and poses biosafety risks in clinical translation. Herein, we choose reduced glutathione (GSH) to quick synthesize gram-scale water-soluble large amino acids mimicking carbon quantum dots (LAAM GSH-CQDs) enriched in steric chain amino acid groups with solubility of up to 2.0 g mL-1. The water-solubility arises from a hexagonal arrangement formed between amino acid groups and water molecules through hydrogen bonding, producing chair-form hexamer hydration layers covering LAAM GSH-CQDs. This endows a noticeable stability against long-term storage and adding electrolytes. Specifically, they exhibit negligible protein absorption, immunogenicity, and hemolysis, with stealth effect, showing an extraordinarily tolerated dose (5000 mg kg-1) in female mice. The rich amino acid groups simultaneously endow them considerable tumor-specific targeting. The loading of first-line chemotherapeutic drug doxorubicin onto LAAM GSH-CQDs through π-π stacking without sacrificing their merits achieves superior tumor inhibition and minimal side effects compared to commercial doxorubicin liposomal. The tumor-targeted drug delivery platform offered by LAAM GSH-CQDs holds significant promise for advancing clinical applications in cancer treatment.