Novel peptide-directed liposomes for targeted combination therapy of breast tumors†
Abstract
Delivery and accumulation of therapeutic drugs into neoplastic cells distant from tumor vessels is a major challenge for antitumor therapy. Herein, we introduced a de novo peptide, p12 (QGSRRRNTVDDWISRRRALC), to conjugate onto the surface of doxorubicin (DOX) and indocyanine green (ICG) co-encapsulated nanoscale liposomes (pLipo-DOX–ICG). The p12 peptide triggered specific binding to CXC chemokine receptor 4 (CXCR4), leading to enhanced cellular uptake and improved accumulation of pLipo-DOX–ICG in CXCR4-overexpressing cancer cells. Moreover, the introduction of ICG molecules endowed pLipo-DOX–ICG with photothermal-induced structural disruption, which may be helpful for the precise and controllable release of doxorubicin at tumor tissue sites in vivo. With these advantages, the constructed pLipo-DOX–ICG demonstrated active targeting behavior for delivery and release of chemotherapeutic drugs, thereby showing much enhanced metastasis inhibition and antitumor efficacy than either drug-containing liposomes without p12 modification or free drugs in breast cancer bearing mice models. Overall, pLipo-DOX–ICG with low toxicity is expected to be a potential therapeutic agent to improve clinical benefits of breast cancer therapies, as well as treatment of a variety of CXCR4-overexpressing malignancies.