Selectively inducing
tumor thrombosis and subsequent
necrosis is a novel and promising antitumor strategy. We have previously designed a targeting procoagulant
protein, called tTF-EG3287, which is a fusion of a truncated
tissue factor (tTF) with
EG3287, a short
peptide against the
neuropilin-1 (NRP1) binding site of
vascular endothelial growth factor-A 165 (VEGF-A 165). However, off-target effects and high-dose requirements limit the further use of tTF-EG3287 in antitumor
therapy. Therefore, we encapsulated tTF-EG3287 into poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl
ethanolamine (PEOz-
DSPE)-modified
liposomes to construct pH-responsive
liposomes as a novel vascular embolization agent, called tTF-
EG3287@
Liposomes. The
liposomes had an average particle size of about 100 nm and showed considerable
drug-loading capacity, encapsulation efficiency, and biocompatibility. Under the stimulation of acidic microenvironments (pH 6.5), the
lipid membrane of tTF-
EG3287@
Liposomes collapsed, and the cumulative drug release rate within 72 h was 83 ± 1.26%. When administered to a mouse model of
hepatocellular carcinoma (HCC), tTF-
EG3287@
Liposomes showed prolonged retention and enhanced accumulation in the
tumor as well as a superior antitumor effec, compared with tTF-EG3287. This study demonstrates the potential of tTF-
EG3287@
Liposomes as a novel embolic agent for solid
tumors and provides a new strategy for
tumor-targeted
infarction therapy.