Construction of l-Carnitine-Modified TPGS Micelles to Achieve Oral Delivery of Camptothecin and Targeted Anticancer Effects

Oral anticancer nanodrugs have recently gained considerable interest due to their advantages of good patient compliance, noninvasiveness, convenience, and repeatable administration. Here, we constructed an l-carnitine-modified α-tocopherol acid poly(ethylene glycol) succinate (Lc-TPGS) oral nanodrug delivery carrier. Studies have shown that Lc-TPGS-based nanodrugs show high stability in simulated gastroenteric fluid and the encapsulation of hydrophobic camptothecin (CPT) in orally administered Lc-TPGS micelles enhances absorption by the intestine through the specific interaction of l-carnitine and the abundantly expressed organic cation transporter 2 (OCTN2). Endocytosed Lc-TPGS-CPT nanodrugs in the intestinal epithelial cells were transcytosed through the endoplasmic reticulum/Golgi pathway into blood circulation in integrity for tumor-targeted delivery. With coumarin 6 or DiR as loaded tracking molecules, in vitro fluorescence imaging and flow cytometry analysis, as well as in vivo imaging, revealed that Lc-TPGS-based nanosystems displayed more efficient cellular uptake and selective accumulation at the tumor site, indicating good tumor-targeting ability. The potential of Lc-TPGS-CPT nanodrugs for effective anticancer activity is demonstrated in vitro. Compared with free CPT and TPGS-CPT nanodrugs, orally administered Lc-TPGS micelles specifically deliver CPT to tumors, efficiently inhibiting the growth of 4T1 tumors with minimal side effects.