title: Hydrophobic penetrating peptide PFVYLI-modified stealth liposomes for doxorubicin delivery in breast cancer therapy.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, ShenYang Pharmaceutical University, ShenYang 110016, China; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar 161006, China.
authors.forename: Defu
authors.initials: D
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: zqdodo@bjmu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers; D004705:Endocytosis; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D020349:Surface Plasmon Resonance
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D009842:Oligopeptides; C547519:prolyl-phenylalanyl-valyl-tyrosyl-leucyl-isoleucine; D004317:Doxorubicin
keywords: Drug delivery; Hydrophobic penetration peptide; Liposome; Nanomedicine; PFVYLI