Background: PEGylation of stealth liposomes elevates their stability and prolongs plasma half-life.
Stealth liposomes modified with targeting ligands are expected to be ideal drug delivery carriers.
Objective: To encapsulate docetaxel in tbFGF (truncated basic fibroblast growth factor)-functionalized liposomes
with mPEG2000-VE (d-α-tocopheryl polyethylene glycol succinate, TPGS2K) and measure their antitumor effects
in vitro and in vivo.
Methods: TPGS2K and COOH-PEG2000-VE were synthesized, and tbFGF was conjugated to COOH-PEG2000-VE
to prepare tbFGF-PEG2000-VE. Then, tbFGF-functionalized liposomes (DTX-tbFGF-LPs) were prepared by inserting
tbFGF-PEG2000-VE into docetaxel liposomes comprising TPGS2K (DTX-PEG-LPs). The stabilities and
drug release profiles of the formulation were evaluated. P-glycoprotein (P-gp) inhibition was measured by ATPase
assay. MTT and cell uptake were measured with B16 cells. A B16 C57BL/6 mouse model was used to
evaluate in vivo antitumor efficacy.
Results: Both DTX-PEG-LPs and DTX-tbFGF-LPs exhibited good stability and sustained drug release. MTT,
flow cytometry, and fluorescence microscopy of B16 cells revealed higher antitumor activity and more efficient
cell uptake for DTX-tbFGF-LPs compared with DTX-PEG-LPs and DTX-LPs. The P-gp ATPase assay showed
that both PEG-LP and tbFGF-PEG-LP formulations inhibited P-gp pump activity in vitro. DTX-tbFGF-LPs had
the highest antitumor efficacy and lowest toxicity in vivo.
Conclusion: Truncated basic fibroblast growth factor-functionalized liposomes with TPGS2K as drug delivery
nanocarriers were effective chemotherapy agents targeting FGFR-overexpressing tumors.