Engineering liposomes and nanoparticles for biological targeting.

Our ability to engineer nanomaterials for biological and medical applications is continuously increasing, and nanomaterial designs are becoming more and more complex. One very good example of this is the drug delivery field where nanoparticle systems can be used to deliver drugs specifically to diseased tissue. In the early days, the design of the nanoparticles was relatively simple, but today we can surface functionalize and manipulate material properties to target diseased tissue and build highly complex drug release mechanisms into our designs. One of the most promising strategies in drug delivery is to use ligands that target overexpressed or selectively expressed receptors on the surface of diseased cells. To utilize this approach, it is necessary to control the chemistry involved in surface functionalization of nanoparticles and construct highly specific functionalities that can be used as attachment points for a diverse range of targeting ligands such as antibodies, peptides, carbohydrates and vitamins. In this review we provide an overview and a critical evaluation of the many strategies that have been developed for surface functionalization of nanoparticles and furthermore provide an overview of how these methods have been used in drug delivery systems.

[1]  C. Redemann,et al.  Synthesis of carboxyacyl derivatives of phosphatidylethanolamine and use as an efficient method for conjugation of protein to liposomes. , 1986, Biochimica et biophysica acta.

[2]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[3]  M. Meldal,et al.  Peptidotriazoles: Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions on Solid-Phase , 2001 .

[4]  G Gregoriadis,et al.  Drug-carrier potential of liposomes in cancer chemotherapy. , 1974, Lancet.

[5]  Ananth Annapragada,et al.  Controlled targeting of liposomal doxorubicin via the folate receptor in vitro. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[6]  G. Denardo,et al.  Production of Soluble ScFvs with C-Terminal-Free Thiol for Site-Specific Conjugation or Stable Dimeric ScFvs on Demand , 2004 .

[7]  John W. Park,et al.  Sterically stabilized anti-HER2 immunoliposomes: design and targeting to human breast cancer cells in vitro. , 1997, Biochemistry.

[8]  M. Alsina,et al.  Physico-chemical characterization of liposomes with covalently attached hepatitis A VP3(101-121) synthetic peptide. , 1998, In Analysis.

[9]  T. Allen,et al.  Ligand-targeted liposomes for cancer treatment. , 2005, Current drug delivery.

[10]  M. Woodle,et al.  Sterically stabilized liposomes. , 1992, Biochimica et biophysica acta.

[11]  Vladimir P Torchilin,et al.  Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers. , 2008, Advanced drug delivery reviews.

[12]  올래프 비. 킨스틀러,et al.  N-terminally chemically modified protein compositions and method , 1995 .

[13]  J. C. Domingo,et al.  Preparation of long-circulating immunoliposomes using PEG-cholesterol conjugates: effect of the spacer arm between PEG and cholesterol on liposomal characteristics. , 2001, Chemistry and physics of lipids.

[14]  R. Schiffelers,et al.  Peptide-targeted PEG-liposomes in anti-angiogenic therapy. , 2003, International journal of pharmaceutics.

[15]  J. Kamps,et al.  Receptor versus non-receptor mediated clearance of liposomes. , 1998, Advanced drug delivery reviews.

[16]  F. Karush,et al.  Attachment of immunoglobulin to liposomal membrane via protein carbohydrate. , 1984, Biochimica et biophysica acta.

[17]  M. Bentley,et al.  Chemistry for peptide and protein PEGylation. , 2002, Advanced drug delivery reviews.

[18]  S. Wise Nanocarriers as an emerging platform for cancer therapy , 2007 .

[19]  T. Andresen,et al.  Oxidative Stability of Liposomes Composed of Docosahexaenoic Acid-Containing Phospholipids , 2007 .

[20]  A. Antony,et al.  The biological chemistry of folate receptors. , 1992, Blood.

[21]  Dae-Duk Kim,et al.  Disaccharide-modified liposomes and their in vitro intracellular uptake. , 2009, International journal of pharmaceutics.

[22]  F. Davis,et al.  Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. , 1977, The Journal of biological chemistry.

[23]  D. Kranz,et al.  Folate receptors as potential therapeutic targets in choroid plexus tumors of SV40 transgenic mice , 1997, Journal of Neuro-Oncology.

[24]  T. Allen,et al.  In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach. , 2001, Biochimica et biophysica acta.

[25]  V. Torchilin,et al.  Comparative studies on covalent and noncovalent immobilization of protein molecules on the surface of liposomes. , 1978, Biochemical and biophysical research communications.

[26]  T. Okada,et al.  Preparation of functional liposomes with peptide ligands and their binding to cell membranes , 2000, Lipids.

[27]  S. Kornfeld,et al.  Structure of the carbohydrate units of IgA1 immunoglobulin. I. Composition, glycopeptide isolation, and structure of the asparagine-linked oligosaccharide units. , 1974, The Journal of biological chemistry.

[28]  Robert J. Lee,et al.  Synthesis of cetuximab-immunoliposomes via a cholesterol-based membrane anchor for targeting of EGFR. , 2007, Bioconjugate chemistry.

[29]  E. Moase,et al.  Attachment of antibodies to sterically stabilized liposomes: evaluation, comparison and optimization of coupling procedures. , 1995, Biochimica et biophysica acta.

[30]  Jennifer A. Prescher,et al.  A strain-promoted [3 + 2] azide-alkyne cycloaddition for covalent modification of biomolecules in living systems. , 2004, Journal of the American Chemical Society.

[31]  T. Honda,et al.  Design of Folate-Linked Liposomal Doxorubicin to its Antitumor Effect in Mice , 2008, Clinical Cancer Research.

[32]  Ulrik B Nielsen,et al.  Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[33]  T. Andresen,et al.  Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release. , 2005, Progress in lipid research.

[34]  T. Ishida,et al.  Recent advances in tumor vasculature targeting using liposomal drug delivery systems , 2009, Expert opinion on drug delivery.

[35]  P. Reaven,et al.  Liposomes enriched in oleic acid are less susceptible to oxidation and have less proinflammatory activity when exposed to oxidizing conditions. , 1998, Journal of lipid research.

[36]  A. Kros,et al.  The chemical modification of liposome surfaces via a copper-mediated [3 + 2] azide-alkyne cycloaddition monitored by a colorimetric assay. , 2006, Chemical communications.

[37]  M S Newman,et al.  Immunogenicity and pharmacokinetic attributes of poly(ethylene glycol)-grafted immunoliposomes. , 1997, Biochimica et biophysica acta.

[38]  Istvan Toth,et al.  Encapsulation of lipopeptides within liposomes: effect of number of lipid chains, chain length and method of liposome preparation. , 2005, International journal of pharmaceutics.

[39]  U. Nielsen,et al.  Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. , 2006, Cancer research.

[40]  F. Ciuchi,et al.  Self-Recognition and Self-Assembly of Folic Acid Salts: Columnar Liquid Crystalline Polymorphism and the Column Growth Process , 1994 .

[41]  V. Torchilin,et al.  A new hydrophobic anchor for the attachment of proteins to liposomal membranes , 1986, FEBS letters.

[42]  F. Martin,et al.  Immunospecific targeting of liposomes to cells: a novel and efficient method for covalent attachment of Fab' fragments via disulfide bonds. , 1981, Biochemistry.

[43]  F. Veronese,et al.  Surface modification of proteins activation of monomethoxy-polyethylene glycols by phenylchloroformates and modification of ribonuclease and superoxide dismutase , 1985, Applied biochemistry and biotechnology.

[44]  J. Benoit,et al.  Design of targeted lipid nanocapsules by conjugation of whole antibodies and antibody Fab' fragments. , 2007, Biomaterials.

[45]  S. Zalipsky Synthesis of an end-group functionalized polyethylene glycol-lipid conjugate for preparation of polymer-grafted liposomes. , 1993, Bioconjugate chemistry.

[46]  E. London,et al.  Interactions between saturated acyl chains confer detergent resistance on lipids and glycosylphosphatidylinositol (GPI)-anchored proteins: GPI-anchored proteins in liposomes and cells show similar behavior. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[47]  G. Marcucci,et al.  Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[48]  Y. Shimada,et al.  Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[49]  M. Finn,et al.  Discovery and characterization of catalysts for azide-alkyne cycloaddition by fluorescence quenching. , 2004, Journal of the American Chemical Society.

[50]  Maruyama,et al.  Possibility of active targeting to tumor tissues with liposomes. , 1999, Advanced drug delivery reviews.

[51]  G. Storm,et al.  Specific targeting with poly(ethylene glycol)-modified liposomes: coupling of homing devices to the ends of the polymeric chains combines effective target binding with long circulation times. , 1993, Biochimica et biophysica acta.

[52]  Luke S. S. Guo,et al.  Sialyl Lewis x Liposomes as a Multivalent Ligand and Inhibitor of E-Selectin Mediated Cellular Adhesion , 1996 .

[53]  O. Melnyk,et al.  Chemoselective acylation of fully deprotected hydrazino acetyl peptides. Application to the synthesis of lipopetides. , 2001, The Journal of organic chemistry.

[54]  V. Torchilin,et al.  p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups. , 2001, Biochimica et biophysica acta.

[55]  J. Weinstein,et al.  Antibody-Mediated Targeting of Liposomes , 1982 .

[56]  R. Schiffelers,et al.  Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[57]  J. Petriz,et al.  A novel strategy affords high-yield coupling of antibody to extremities of liposomal surface-grafted PEG chains. , 1999, Biochimica et biophysica acta.

[58]  B. Frisch,et al.  Synthesis of an amphiphilic tetraantennary mannosyl conjugate and incorporation into liposome carriers. , 2003, Bioorganic & medicinal chemistry letters.

[59]  J. Clamp,et al.  THE PERIODATE OXIDATION OF AMINO ACIDS WITH REFERENCE TO STUDIES ON GLYCOPROTEINS. , 1965, The Biochemical journal.

[60]  K. Petry,et al.  Annexin A5-functionalized liposomes for targeting phosphatidylserine-exposing membranes. , 2009, Bioconjugate chemistry.

[61]  Jie Xue,et al.  Biomimetic glycoliposomes as nanocarriers for targeting P-selectin on activated platelets. , 2007, Bioconjugate chemistry.

[62]  D. Lichtenberg,et al.  Peroxidation of liposomal palmitoyllinoleoylphosphatidylcholine (PLPC), effects of surface charge on the oxidizability and on the potency of antioxidants. , 2003, Chemistry and physics of lipids.

[63]  P. Wils,et al.  Folate-targeted, cationic liposome-mediated gene transfer into disseminated peritoneal tumors , 2002, Gene Therapy.

[64]  P. Low,et al.  Peptide-Mediated Release of Folate-Targeted Liposome Contents from Endosomal Compartments1 , 1996 .

[65]  E. C. Beuvery,et al.  Comparison of four bifunctional reagents for coupling peptides to proteins and the effect of the three moieties on the immunogenicity of the conjugates. , 1989, Journal of immunological methods.

[66]  D. Tzemach,et al.  Targeting folate receptor with folate linked to extremities of poly(ethylene glycol)-grafted liposomes: in vitro studies. , 1999, Bioconjugate chemistry.

[67]  B. Frisch,et al.  Effect of synthetic lipopeptides formulated in liposomes on the maturation of human dendritic cells. , 2005, Molecular immunology.

[68]  J. Kamps,et al.  The influence of repeated injections on pharmacokinetics and biodistribution of different types of sterically stabilized immunoliposomes. , 2003, Biochimica et biophysica acta.

[69]  H. Yanagie,et al.  Liposomes Bearing Polyethyleneglycol-Coupled Transferrin with Intracellular Targeting Property to the Solid Tumors In Vivo , 2001, Pharmaceutical Research.

[70]  T M Allen,et al.  In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. , 1998, Cancer research.

[71]  T. Seki,et al.  Uptake characteristics of liposomes by rat alveolar macrophages: influence of particle size and surface mannose modification , 2007, The Journal of pharmacy and pharmacology.

[72]  B. Frisch,et al.  Synthesis of short polyoxyethylene-based heterobifunctional cross-linking reagents. Application to the coupling of peptides to liposomes. , 1996, Bioconjugate chemistry.

[73]  M. Wilchek,et al.  A simplified method for the preparation of succinimidyl carbonate polyethylene glycol for coupling to proteins. , 1993, Bioconjugate chemistry.

[74]  O. Melnyk,et al.  Solid-Phase Functionalization of Peptides by an α-Hydrazinoacetyl Group , 2003 .

[75]  L. Huang,et al.  Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol)s conjugated at their distal terminals to monoclonal antibodies. , 1995, Biochimica et biophysica acta.

[76]  R. Offord,et al.  Site-specific attachment of functionalized poly(ethylene glycol) to the amino terminus of proteins. , 1996, Bioconjugate chemistry.

[77]  V. Torchilin,et al.  Preservation of antimyosin antibody activity after covalent coupling to liposomes. , 1979, Biochemical and biophysical research communications.

[78]  K. Nohga,et al.  Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner , 2003, British Journal of Cancer.

[79]  J. Weinstein,et al.  Antibody-mediated targeting of liposomes. Binding to lymphocytes does not ensure incorporation of vesicle contents into the cells. , 1978, Biochimica et biophysica acta.

[80]  K. Geoghegan,et al.  Site-directed conjugation of nonpeptide groups to peptides and proteins via periodate oxidation of a 2-amino alcohol. Application to modification at N-terminal serine. , 1992, Bioconjugate chemistry.

[81]  U. Bakowsky,et al.  Targetability of novel immunoliposomes prepared by a new antibody conjugation technique. , 1999, International journal of pharmaceutics.

[82]  T. Andresen,et al.  Secretory phospholipase A2 as a tumor-specific trigger for targeted delivery of a novel class of liposomal prodrug anticancer etherlipids. , 2004, Molecular cancer therapeutics.

[83]  A. Blair,et al.  [20] Preparation of antibody-linked cytotoxic agents , 1983 .

[84]  Philip S Low,et al.  Folate-mediated delivery of macromolecular anticancer therapeutic agents. , 2002, Advanced drug delivery reviews.

[85]  R. Gaspar,et al.  Use of the Post-Insertion Technique to Insert Peptide Ligands into Pre-Formed Stealth Liposomes with Retention of Binding Activity and Cytotoxicity , 2002, Pharmaceutical Research.

[86]  J W Hershey,et al.  Methyl 4-mercaptobutyrimidate as a cleavable cross-linking reagent and its application to the Escherichia coli 30S ribosome. , 1973, Biochemistry.

[87]  H. Gabius Endogenous lectins in tumors and the immune system. , 1987, Cancer investigation.

[88]  David H. Thompson,et al.  Novel Flexible and Rigid Tetraether Acyclic and Macrocyclic Bisphosphocholines: Synthesis and Monolayer Properties , 2000 .

[89]  B. Frisch,et al.  Differential reactivity of maleimide and bromoacetyl functions with thiols: application to the preparation of liposomal diepitope constructs. , 2000, Bioconjugate chemistry.

[90]  He Zhang,et al.  Tumor-targeted PE38KDEL delivery via PEGylated anti-HER2 immunoliposomes. , 2009, International journal of pharmaceutics.

[91]  R. I. Jølck,et al.  Solid-phase synthesis of PEGylated lipopeptides using click chemistry. , 2010, Bioconjugate chemistry.

[92]  E. Moase,et al.  Use of the post-insertion method for the formation of ligand-coupled liposomes. , 2002, Cellular & molecular biology letters.

[93]  Makoto Murakami,et al.  Secretory phospholipase A2. , 2004, Biological & pharmaceutical bulletin.

[94]  I. Rubinstein,et al.  VIP receptors as molecular targets of breast cancer: implications for targeted imaging and drug delivery. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[95]  C. Demangel,et al.  Identification of a peptide blocking vascular endothelial growth factor (VEGF)‐mediated angiogenesis , 2000, The EMBO journal.

[96]  S. Matile,et al.  Direct evidence for the importance of hydrophobic mismatch for cell membrane recognition , 1999 .

[97]  G. Koning,et al.  Targeting liposomes to tumor endothelial cells for neutron capture therapy. , 2004, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[98]  L. Huang,et al.  Monoclonal antibody covalently coupled with fatty acid. A reagent for in vitro liposome targeting. , 1980, The Journal of biological chemistry.

[99]  M. Merkx,et al.  Protein-liposome conjugates using cysteine-lipids and native chemical ligation. , 2007, Bioconjugate chemistry.

[100]  T. Ishida,et al.  A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs , 1999, FEBS letters.

[101]  R. Mehvar Recent trends in the use of polysaccharides for improved delivery of therapeutic agents: pharmacokinetic and pharmacodynamic perspectives. , 2003, Current pharmaceutical biotechnology.

[102]  T. Allen,et al.  Ligand-targeted liposomal anticancer drugs. , 2003, Progress in lipid research.

[103]  P. Low,et al.  Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis. , 1994, The Journal of biological chemistry.

[104]  D. Auguste,et al.  The role of antibody synergy and membrane fluidity in the vascular targeting of immunoliposomes. , 2010, Biomaterials.

[105]  J Szebeni,et al.  Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: the challenges ahead. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[106]  Morten Meldal,et al.  Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. , 2002, The Journal of organic chemistry.

[107]  J. Kamps,et al.  Selective transfer of a lipophilic prodrug of 5-fluorodeoxyuridine from immunoliposomes to colon cancer cells. , 1999, Biochimica et biophysica acta.

[108]  T. Muir,et al.  Synthesis of proteins by native chemical ligation. , 1994, Science.

[109]  S. Muller,et al.  Immunogenicity of new heterobifunctional cross-linking reagents used in the conjugation of synthetic peptides to liposomes. , 1996, Journal of immunological methods.

[110]  K. Meerovitch,et al.  A novel RGD antagonist that targets both alphavbeta3 and alpha5beta1 induces apoptosis of angiogenic endothelial cells on type I collagen. , 2003, Vascular pharmacology.

[111]  R K Jain,et al.  Physiologically based pharmacokinetic model for specific and nonspecific monoclonal antibodies and fragments in normal tissues and human tumor xenografts in nude mice. , 1994, Cancer research.

[112]  K. Meerovitch,et al.  A novel RGD antagonist that targets both αvβ3 and α5β1 induces apoptosis of angiogenic endothelial cells on type I collagen , 2003 .

[113]  P. Low,et al.  Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro. , 1995, Biochimica et biophysica acta.

[114]  V. Zurawski,et al.  Cellular localization of the folate receptor: potential role in drug toxicity and folate homeostasis. , 1992, Cancer research.

[115]  B. Frisch,et al.  Targeted liposomes: convenient coupling of ligands to preformed vesicles using "click chemistry". , 2006, Bioconjugate chemistry.

[116]  Xue-Long Sun,et al.  Chemically-selective surface glyco-functionalization of liposomes through Staudinger ligation. , 2009, Chemical communications.

[117]  S. Kornfeld,et al.  Structure of the carbohydrate units of IgA1 immunoglobulin. II. Structure of the O-glycosidically linked oligosaccharide units. , 1974, The Journal of biological chemistry.

[118]  C HISCOCK,et al.  YELLOW NAILS AND LYMPHOEDEMA. , 1964, Lancet.

[119]  A. Herrmann,et al.  Molecular rods with oligospiroketal backbones as anchors in biological membranes. , 2009, Angewandte Chemie.

[120]  T. Okada,et al.  Synthesis of a novel lipopeptide with α-melanocyte-stimulating hormone peptide ligand and its effect on liposome stability , 1999, Lipids.

[121]  D. Marsh,et al.  Intrinsic curvature in normal and inverted lipid structures and in membranes. , 1996, Biophysical journal.

[122]  R. Wrigglesworth,et al.  A new reagent which may be used to introduce sulfhydryl groups into proteins, and its use in the preparation of conjugates for immunoassay. , 1983, Analytical biochemistry.

[123]  T. Seo,et al.  1,3-Dipolar cycloaddition of azides with electron-deficient alkynes under mild condition in water , 2004 .

[124]  S. Hirota,et al.  Biodistribution of liposomes containing synthetic galactose-terminated diacylglyceryl-poly(ethyleneglycol)s. , 1997, Biochimica et biophysica acta.

[125]  Y. Barenholz,et al.  Effect of grafted PEG on liposome size and on compressibility and packing of lipid bilayer. , 2005, Chemistry and physics of lipids.

[126]  M. Woodle,et al.  Peptide attachment to extremities of liposomal surface grafted PEG chains: preparation of the long-circulating form of laminin pentapeptide, YIGSR. , 1995, Bioconjugate chemistry.

[127]  A. Blair,et al.  Preparation of antibody-linked cytotoxic agents. , 1983, Methods in enzymology.

[128]  J. Reubi In Vitro Identification of VIP Receptors in Human Tumors: Potential Clinical Implications , 1996, Annals of the New York Academy of Sciences.

[129]  J C Reubi,et al.  In vitro identification of vasoactive intestinal peptide receptors in human tumors: implications for tumor imaging. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[130]  G. Scherphof,et al.  Uptake and processing of immunoglobulin-coated liposomes by subpopulations of rat liver macrophages. , 1988, Biochimica et biophysica acta.

[131]  Luke G Green,et al.  A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. , 2002, Angewandte Chemie.

[132]  Andrew D. Miller,et al.  Targeting the urokinase plasminogen activator receptor with synthetic self-assembly nanoparticles. , 2009, Bioconjugate chemistry.

[133]  T. Allen,et al.  A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells. , 1995, Biochimica et biophysica acta.

[134]  Nagasuma R. Chandra,et al.  CancerLectinDB: a database of lectins relevant to cancer , 2008, Glycoconjugate Journal.

[135]  Andrea J. Hanson,et al.  Mechanistic studies of the triggered release of liposomal contents by matrix metalloproteinase-9. , 2008, Journal of the American Chemical Society.

[136]  V. Torchilin,et al.  Tumor-specific anti-nucleosome antibody improves therapeutic efficacy of doxorubicin-loaded long-circulating liposomes against primary and metastatic tumor in mice. , 2009, Molecular pharmaceutics.

[137]  S. Simões,et al.  Design of peptide-targeted liposomes containing nucleic acids. , 2010, Biochimica et biophysica acta.

[138]  V. Torchilin Liposomes as targetable drug carriers. , 1985, Critical reviews in therapeutic drug carrier systems.

[139]  F. Martin,et al.  Irreversible coupling of immunoglobulin fragments to preformed vesicles. An improved method for liposome targeting. , 1982, The Journal of biological chemistry.

[140]  D. Fisher,et al.  PEGylation of cytokines and other therapeutic proteins and peptides: the importance of biological optimisation of coupling techniques. , 1998, International journal of hematology.

[141]  D. Pacchioni,et al.  Antitumoral activity of liposomes and immunoliposomes containing 5-fluorouridine prodrugs. , 1997, Journal of pharmaceutical sciences.

[142]  P. Jap,et al.  Design of immunoliposomes directed against human ovarian carcinoma. , 1995, Biochimica et biophysica acta.

[143]  U. Massing,et al.  Studies on protein-liposome coupling using novel thiol-reactive coupling lipids: influence of spacer length and polarity. , 2001, Bioconjugate chemistry.

[144]  N. Mullah,et al.  New chemoenzymatic approach to glyco-lipopolymers: practical preparation of functionally active galactose–poly(ethylene glycol)–distearoylphosphatidic acid (Gal–PEG–DSPA) conjugate , 1999 .

[145]  O. Melnyk,et al.  Anchorage of synthetic peptides onto liposomes via hydrazone and alpha-oxo hydrazone bonds. preliminary functional investigations. , 2005, Bioconjugate chemistry.

[146]  E. Chang,et al.  Systemic p53 Gene Therapy of Cancer with Immunolipoplexes Targeted by Anti-Transferrin Receptor scFv , 2001, Molecular medicine.

[147]  O. G. Mouritsen,et al.  Enzymatic release of antitumor ether lipids by specific phospholipase A2 activation of liposome-forming prodrugs. , 2004, Journal of medicinal chemistry.

[148]  U. Nielsen,et al.  Tumor targeting using anti-her2 immunoliposomes. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[149]  C. Bertozzi,et al.  Cell surface engineering by a modified Staudinger reaction. , 2000, Science.

[150]  Wim E Hennink,et al.  Nonnatural amino acids for site-specific protein conjugation. , 2009, Bioconjugate chemistry.

[151]  G. Denardo,et al.  Production of soluble ScFvs with C-terminal-free thiol for site-specific conjugation or stable dimeric ScFvs on demand. , 2004, Bioconjugate chemistry.

[152]  P. Low,et al.  Diplasmenylcholine−Folate Liposomes: An Efficient Vehicle for Intracellular Drug Delivery† , 1998 .

[153]  R. Marchant,et al.  Synthesis and characterization of oligomaltose-grafted lipids with application to liposomes. , 2002, Journal of colloid and interface science.