title: In vitro optimization of liposomal nanocarriers prepared from breast tumor cell specific phage fusion protein.
abstract: Fusion proteins created by phage display peptides with tumor cell specificity and the pVIII major coat protein of filamentous phages have been explored recently as a simple and cost-effective means for preparing tumor-targeted liposomes that improve the cytotoxicity of anticancer drugs in vitro. The next step in the development of this approach is the optimization of the liposome composition for the maximum targeting activity and subsequent testing in vivo. This study aimed to investigate the impact of preparation protocols, lipid composition and phage protein content on the targeting efficiency of phage protein-modified liposomes. Analysis of size, zeta potential and morphology was used to investigate the effect of preparation protocols on the stability and homogeneity of the phage liposomes. A previously developed coculture targeting assay and a factorial design approach were used to determine the role of lipid composition of the liposomal membrane on the target cell specificity of the phage liposomes. Western blot combined with proteinase K treatment detected the orientation of targeted phage protein in liposomal membrane. Phage protein, DPPG and PEG(2k)-PE showed positive effects on target specificity of phage liposomes. The results served to identify optimal formulation that offer an improved liposomal affinity for target tumor cells over the non-optimized formulation.
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Nikita
authors.initials: N
authors.lastname: Kulkarni
authors.forename: Deepa
authors.initials: D
authors.lastname: Bedi
authors.forename: Gerard G M
authors.initials: GG
authors.lastname: D'Souza
authors.forename: Brigitte
authors.initials: B
authors.lastname: Papahadjopoulos-Sternberg
authors.forename: Valery A
authors.initials: VA
authors.lastname: Petrenko
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D051379:Mice; D008854:Microscopy, Electron; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D019151:Peptide Library; D013050:Spectrometry, Fluorescence; D013499:Surface Properties; D014760:Viral Fusion Proteins / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D019151:Peptide Library; D014760:Viral Fusion Proteins