Hydrophobic penetrating peptide PFVYLI-modified stealth liposomes for doxorubicin delivery in breast cancer therapy.

Based on the hydrophobic interaction with biomembranes, PFVYLI (PFV), a hydrophobic penetration peptide (HPP), was initially introduced to modify doxorubicin-loaded stealth-sustained liposomes (PFV-SSLs-DOX) against different breast cancer cell phenotypes irrespective of their receptor expression or antigen presence. The physicochemical characteristics of PFV-SSLs were determined with approximately 100 nm size, satisfactory distribution and high encapsulation. In addition, drug release experiments demonstrated that modification with PFV has a negligible influence on the release profile of liposomes. Surface plasmon resonance (SPR) analysis revealed that PFV-modified liposomes could increase the binding proportion of PFV-SSLs with a model cell membrane. It was demonstrated that modification with PFV highly facilitated the intracellular delivery of DOX-loaded liposomes and enhanced cytotoxicity via a hydrophobic interaction. An endocytosis inhibition assay revealed a combination of cellular internalization mechanisms for PFV-SSLs involving lipid raft and clathrin-mediated endocytosis in a temperature-dependent manner. The PFV-modified liposomes displayed more lasting accumulation in the tumor and better tumor growth inhibition with relatively low systemic and cardiac toxicity. In conclusion, PFV-SSLs might be a promising delivery system for the delivery of different therapeutic or imaging agents to heterogeneous tumors. More significantly, this study provides a new perspective on developing HPP-modified drug delivery system for antitumor therapy.