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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.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Cai D,Gao W,He B,Dai W,Zhang H,Wang X,Wang J,Zhang X,Zhang Q

doi

10.1016/j.biomaterials.2013.11.088

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

2283-94

issue

7

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(13)01454-3

journal_volume

35

pub_type

杂志文章

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