2.2.2. Protein-Targeted Liposomes Qi et al. described a novel antineoplastic liposomal agent, liposomal saposin C [132]. Development of this agent is based on the observation that patients suffering from lysosomal storage diseases frequently have saposin C deficiencies leading to accumulation of toxic glycosylceramide sphingolipids [133] and that saposin Inhibitors,research,lifescience,medical C inserts into negatively charged membranes at acidic pH [134]. They prepared a saposin C-DOPS conjugate which assembled as 190nm liposomes under sonication at acidic pH. Tumor targeting is based on activation of membrane fusion

domains of saposin C at the acidic pH in tumors leading to its internalization and glycosylceramide-induced apoptosis. Intravenous Inhibitors,research,lifescience,medical injection into neuroblastoma xenograft- bearing mice led to apoptosis induction in tumors and tumor growth inhibition without systemic toxicity. BAFF (B cell activating factor) is a cytokine whose receptor is overexpressed in B-cell lymphomas, conjugation of a BAFF mutant to vincristine-loaded PEGylated liposomes increased the survival of lymphoma-bearing mice over untargeted vincristine-loaded liposomes or free drug [35]. Inhibitors,research,lifescience,medical Cancer cells overexpress transferrin receptors [135] making the glycoprotein, transferrin or antibodies to transferrin receptor, suitable ligands for tumor targeting [136]. Addition of transferrin to the surface of PEGylated oxaliplatin-loaded

liposomes increased tumor accumulation over free oxaliplatin or untargeted liposomes leading to the highest tumor growth inhibition against C26 colon carcinoma-bearing mice [36]. In parallel to these studies, conjugation of transferrin to doxorubicin-loaded liposomes resulted in higher doxorubicin delivery to tumors and tumor growth inhibition over untargeted doxorubicin-loaded Inhibitors,research,lifescience,medical liposomes [103]. 2.2.3. Peptide-Targeted Liposomes More and more tumor-specific ligands are being identified by combinatorial screening of bacteriophage-borne peptide libraries, phage display biopanning. This is a strategy whereby

the recombinant SAR405838 in vitro virions Inhibitors,research,lifescience,medical able to bind cancer cells in vitro or tumors in vivo are purified before identification of the peptide and its use for many targeted drug delivery, allowing identification of peptides specific for cancer cells, tumor vasculature or both (reviewed in [137]). We previously described the selective exposure of nucleohistones by cancer cells effective cancer therapy of antinuclear-targeted doxorubicin-loaded liposomes [32]. In good agreement with these studies, Wang et al. reported tumor targeting of doxorubicin-loaded liposomes harboring the histone H1-specific peptide ApoPep-1 [138]. This peptide is selectively presented at the surface of tumor cells due to spontaneous apoptosis in avascular tumors. ApoPep-1 conjugation to doxorubicin-loaded liposomes led to superior doxorubicin distribution in lung xenografts and better tumor growth inhibition over untargeted liposomes.