A membrane penetrating cyclic lipopeptide based nanocarrier for cancer drug delivery

Abstract

Herein, the cyclic lipopeptide CLP5 with 1,3,4-oxadiazole and tertiary amine structures was developed to address issues in tumor chemotherapy like non-specificity, drug resistance, and poor bioavailability. CLP5 not only exhibited anticancer activity through membrane breaking and targeting caspase-3, but also self-assembled into stable spherical aggregates, which encapsulated doxorubicin to form the CLP5@DOX nanomedicine. The encapsulation efficiency of CLP5 for doxorubicin was 81.46 ± 3.23%. The CLP5@DOX nanomedicine exhibited sustained DOX release and pH responsiveness. In vitro experiments showed that the CLP5@DOX nanomedicine not only had high membrane penetrating activity to induce cancer cell apoptosis, but also had low toxicity and high serum stability. Animal experiments showed that the CLP5@DOX nanomedicine could effectively inhibit tumor growth while reducing the adverse reactions and toxicity of DOX. Molecular docking experiments showed that CLP5 could activate caspase-3 to target the apoptosis pathway. In conclusion, CLP5 has high potential as a drug carrier for clinical cancer treatment.