Combinations of drugs promoting anti-angiogenesis and apoptosis effects are meaningful for
cancer therapy. In the present study, dual
peptides-modified
liposomes were designed by attaching two receptor-specific
peptides, specifically
low-density lipoprotein receptor-related
protein receptor (Angiopep-2) and
neuropilin-1 receptor (tLyP-1) for
brain tumor targeting and
tumor penetration.
Vascular endothelial growth factor (
VEGF)
siRNA and chemotherapeutic
docetaxel (DTX) were chosen as the two payloads because
VEGF is closely associated with angiogenesis, and DTX can kill
tumor cells efficiently. Binding to
glioma cells, co-delivery of
siRNA and DTX in human
glioblastoma cells (U87 MG) and murine brain microvascular endothelial cells (BMVEC),
VEGF gene silencing, antiproliferation and anti-
tumor effects of the dual
peptides-modified
liposomes were evaluated in vitro and in vivo. The dual
peptides-modified
liposomes persisted the binding ability to
glioma cells, enhanced the internalization via specific receptor mediated endocytosis and tissue penetration, thus the dual
peptides-modified
liposomes loading
VEGF siRNA and DTX possessed stimulative gene silencing and antiproliferation activity compared with non-modified and single
peptide-modified
liposomes. The co-delivery research revealed different intracellular behavior of hydrophilic large molecular and lipophilic small molecule, the former involves endocytosis and subsequent escape of endosome/lysosomes, while the latter experiences passive diffusion of lipophilic small drugs after its release. Furthermore, the dual
peptides-modified
liposomes showed superiority in anti-
tumor efficacy, combination of anti-angiogenesis by
VEGF siRNA and apoptosis effects by DTX, after both intratumor and system application against mice with U87 MG
tumors, and the treatment did not activate system-associated toxicity or the innate immune response. Combination with the dual
peptides-guided
tumor homing and penetration, the dual
peptides-modified
liposomes provide a strategy for effective targeting delivery of
siRNA and DTX into the
glioma cell and inhibition of
tumor growth in a synergistic manner.