LAUSR

BACKGROUND PEGylation of stealth liposomes elevates their stability and prolongs plasma halflife. 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-PEGLPs 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.