Reimaging biological barriers affecting distribution and extravasation of PEG/peptide- modified liposomes in xenograft SMMC7721 tumor

Liposomes, as one of the most successful nanotherapeutics, have a major impact on many biomedical areas. In this study, we performed laser scanning confocal microscope (LSCM) and immunohistochemistry (IHC) assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptide-conjugated active targeting liposomes (GE11-TLs) in SMMC7721 xenograft model. According to classification of individual cell types in high resolution images, biodistribution of macrophages, tumor cells, cells with high epidermal growth factor receptor (EGFR) expression and interstitial matrix in tumor microenvironment, in addition, their impacts on intra-tumor penetration of GE11-TLs were estimated. Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts. Tumor angiogenesis was of great heterogeneity from the periphery to the center region. However, the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs. We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drug delivery. A reported EGFR-targeted peptide GE11 was employed to modify PEGylated liposomes. The distribution and extravasation of GE11-TLs in SMMC7721 HCC xenograft model are well investigated. EGFR positive interstitial cells in tumor microenvironment generate the dominant barrier for deeper permeation for GE11-TLs, though collagen I is the major abundant interstitial matrix in SMMC7721 tumor. [Display omitted]