Tumor-Penetrating Peptide Mediation: An Effective Strategy for Improving the Transport of Liposomes in Tumor Tissue

Currently, the inefficient transport of liposomes in tumor tissue hinders their clinical application. Tumor-penetrating peptides (TPP) are a series of targeting peptides with the function of penetrating tumor blood vessels and tumor stroma. This work aimed to improve the penetration of liposomes in tumor tissues by TPP modification, thereby enhancing the antitumor effect. First, RPARPAR, a TPP, was modified to the surface of liposomes loaded with doxorubicin. The RPARPAR-modified liposomes (RPA-LP) and unmodified liposomes (LP) showed spherical morphology with average sizes about 90 nm. RPA-LP exhibited remarkably increased cellular accumulation by PC-3 tumor cells than LP as evidenced by the cellular uptake test. The in vivo imaging study confirmed that RPARPAR modification significantly increased the liposome accumulation in subcutaneous tumor tissues. RPA-LP could penetrate through tumor blood vessels and tumor stroma and into the deep tumor tissues as evidence by the immunofluorescence staining analysis. The cytotoxicity of RPARPAR-modified doxorubicin liposomes (RPA-LP-DXR) is considerably increased compared with that of doxorubicin liposomes (LP-DXR). The RPA-LP-DXR also showed significantly (p < 0.005) stronger growth-inhibiting effect on tumor than LP-DXR, possibly due to the tumor-Penetrating ability of RPA-LP and targeted killing of tumor cells. This study proved that TPP mediation may be an effective strategy for improving the transport of liposomes in tumor tissue.