Size effect on tumor treatment with PEGylated liposomal drugs in a tumor-bearing mouse model

Objectives PEGylated liposomes are important drug carriers, which can passively target tumor by enhanced permeability and retention effect in neoplasm lesions. This study evaluated the influence of tumor size on the therapeutic efficacy of In-111 and/or vinorelbine (VNB)-encapsulated PEGylated liposomes in a C26/tk-luc colon carcinoma-bearing mouse model.

Methods PEGylated liposomes (NanoX) and those encapsulated with VNB (NanoVNB) were labeled with In-111 to afford InNanoX or InVNBL. BALB/c mice bearing C26/tk-luc tumors (small, 58.4 ± 8.0 mm³; large, 102.4 ± 22.0 mm³) in the right dorsal flank were individually administered intravenously with NanoX, NanoVNB, InNanoX or InVNBL 3 times in 2 weeks. The therapeutic efficacy was evaluated by body weight loss, tumor growth inhibition and survival fraction. The scintigraphic imaging was also performed during the period of treatment.

Results The radiochemical purity of InNanoX and InVNBL were both > 90%. Biodistribution studies showed high tumor uptake since 24 h post injection (p.i.) of InVNBL, especially in the small-tumor bearing mice. In both small-tumor and large-tumor mouse models, mice treated with InVNBL showed the best tumor growth inhibition rate and the highest survival rate compared with those treated with other drugs. All liposomal drugs showed better therapeutic efficacy in mice bearing small tumors than those bearing large tumors. InVNBL-SPECT imaging also revealed significant tumor targeting, especially in small-tumor bearing mice, during the period of treatment.

Conclusions This study demonstrates that InVNBL is a potent antitumor agent especially in the small-tumor bearing mouse model. The results suggest that PEGylated liposomal drugs may be most valuable for the treatment initiated at the early stage of tumor’s growth or tumor metastases