The same group also developed trilysinoyl oleyamide (trilysine peptide linked to oleyamine by a peptide

bond) based PEGylated liposomes for codelivery of Mcl-1 siRNA and the histone deacytylase inhibitor suberoylanilide hydroxamic acid (SAHA) [247]. Intravenous administration increased the tumor growth delay compared to liposomes with SAHA and an irrelevant siRNA. Likewise, Xiao and coworkers used targeted Inhibitors,research,lifescience,medical liposomes to BKM120 molecular weight codeliver doxorubicin and DNA encoding a dominant mutant of survivin [248]. Liposomes were targeted by a truncated basic fibroblast growth factor (tbFGF) peptide recognizing the bFGF receptor upregulated in lung cancers and contained doxorubicin and pDNA encoding for a dominant negative mutant of survivin to counter survivin-mediated Inhibitors,research,lifescience,medical apoptosis resistance [249]. Their codelivery produced a higher therapeutic efficacy against Lewis lung carcinoma tumors than liposomes with either agent alone. A further step in combination of an antineoplastic agent with modulation of drug resistance was achieved recently by Minko and coworkers [250] by formulation of peptide-targeted liposomes containing doxorubicin or cisplatin together with oligonucleotides against the two main drug resistance mechanisms Bcl-2 and MDR1. The efficacy of this “combined targeted chemo and gene therapy” system was evaluated in xenografts established from

human ovarian malignant ascites. Inhibitors,research,lifescience,medical While inclusion of either Bcl-2 or MDR1 antisense oligonucleotides in cisplatin or doxorubicin-loaded targeted liposomes decreased primary tumor volume and intraperitoneal metastases load, further inhibition of tumor growth inhibition Inhibitors,research,lifescience,medical was obtained with targeted liposomes containing

doxorubicin or cisplatin, Bcl-2 and MDR1 antisense oligonucleotides together with complete Inhibitors,research,lifescience,medical prevention of the development of detectable intraperitoneal metastases or ascites. Interestingly, Minko et al. proposed this system as a platform for personalized cancer therapy with liposomal formulations containing antisense oligonucleotides targeting individually relevant resistance mechanism. Sawant et al. coloaded PEGylated liposomes with a palmitoyl-ascorbate conjugate and paclitaxel [251]. The therapeutic benefit of the coloading against 4T1 mammary carcinoma Oxalosuccinic acid was evident at 10mg/kg compared to palmitoyl-ascorbate or paclitaxel-loaded liposomes. Atu027 (Silence Therapeutics, London, UK) is a liposomal formulation of siRNA against protein kinase N3, a downstream effector of the mitogenic PI3K/PTEN pathway involved in prostate cancer metastasis [252, 253]. This formulation was composed of 2′-O-methyl-stabilized siRNA encapsulated in cationic liposomes (50mol% cationic lipid -L-arginyl-2,3-L-diaminopropionic acid-N-palmitoyl-N-oleyl-amide trihydrochloride (AtuFECT01), 49mol% co-lipid 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE), and 1mol% DSPE-PEG2000) [253].