Development of ligand-targeted liposomes for cancer therapy
ABSTRACT The continued evolution of targeted liposomal therapeutics has resulted in new agents with remarkable antitumour efficacy and relatively mild toxicity profiles. A careful selection of the ligand is necessary to reduce immunogenicity, retain extended circulation lifetimes, target tumour-specific cell surface epitopes, and induce internalisation and subsequent release of the therapeutic substance from the liposome. Methods for assembling targeted liposomes, including a novel micellar insertion technology, for incorporation of targeting molecules that efficiently transforms a non-targeted liposomal therapeutic to a targeted one, greatly assist the translation of targeted liposome technology into the clinic. Targeting strategies with liposomes directed at solid tumours and vascular targets are discussed. The authors believe the development of ligand-targeted liposomes is now in the advanced stage and offers unique and important advantages among other targeted therapies. Anti-HER2 immunoliposomal doxorubicin is awaiting Phase I clinical trials, the results of which should provide new insights into the promise of ligand-targeted liposomal therapies.
- SourceAvailable from: Julio Coll
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- "In the liposome field, newer improved therapies based on the use of immunoliposomes containing chemotherapeutic agents are emerging. For instance, the conjugation of complete or fragmented antibodies to liposomes has resulted in the next generation of delivery drugs (Noble et al., 2004; Park et al., 1997). Thus several anticancer therapies targeting members of the epidermal growth factor receptor, such as the protooncogene HER2 (ErbB2), "
ABSTRACT: In this study, melittin, a well-characterized pore-forming lytic amphiphilic peptide susceptible to be vehiculized in lipid membranes, has been utilized to study their anti-viral properties. For this purpose, an assay based on melittin loaded-immunoliposomes previously described by our group was adapted to antiviral purposes by means of monoclonal antibodies targeting the surface G glycoprotein of the fish viral haemorrhagic septicemia rhabdovirus (VHSV). We also studied the antiviral action of these immunoliposomes in vitro and the results showed that they are capable of inhibiting the VHSV infectivity by 95.2% via direct inactivation of the virus. Furthermore, the inhibition of the infectivity when treatments were added at different times post-infection and the analysis of the infection foci sizes suggested altogether that they also act by reducing the VHSV spread in cell culture and by killing the infected cells which express the G glycoprotein in their plasmatic membranes.Antiviral research 12/2012; 97(2). DOI:10.1016/j.antiviral.2012.12.004 · 3.94 Impact Factor
- "In principle, any target binding biological unit can be used, and antibodies or antibody fragments, vitamins, glycoproteins, peptides, oligonucleotides, polysaccharides and others have been attached to liposomes to this effect. Due to their high specificity, liposomes with antibodies attached to their surface as targeting ligands, the so-called immunoliposomes, have emerged as one of the most promising classes for medical applications     . Historically, the first example of an immunoliposome (IL) was prepared by Torchilin and used to localize in acute canine myocardial infarction . "
Article: Immunoliposomes[Show abstract] [Hide abstract]
ABSTRACT: Since their discovery by Bangham about 50 years ago, liposomes have become promising tools in drug delivery systems. This has increased the therapeutic index of many drugs, and offers improved drug targeting and controlled release. In order to further improve the specificity of liposomes for malignant tissues, targeted liposomal formulations have been developed which represent the next step of liposomal drug delivery in medical treatment. Antibodies and antibody fragments are the most widely used targeting moieties for liposomes due to the high specificity for their target antigens. This has given rise to a new class of drug delivery vehicles, the so-called immunoliposomes. Immunoliposomes are generated by coupling of antibodies to the liposomal surface and allow for an active tissue targeting through binding to tumor cell-specific receptors. Such antibody modified liposomes are attracting great interest for their potential use in specific drug delivery to cancer cells, gene therapy, drug delivery through blood brain barrier, or molecular imaging. Thus far, immunoliposomes show promising results in vitro and in vivo and appear to be effective systems for improvements in cancer treatment. This review covers the literature of the past decade with special emphasis on in vitro and in vivo studies.Current Medicinal Chemistry 11/2012; 19(11):5239–5277. DOI:10.1007/978-3-642-01147-4_31 · 3.85 Impact Factor
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- "Passive targeting implies that the enhanced permeability and retention effect (EPR effect), which characterizes malignant tissues, allows the passive accumulation of encapsulated drugs to tumor sites13, 14 . Active targeting involves tagging the drug vehicle with a ligand and allows it to specifically sequester in the targeted tumor15, 16. Among the various ligands, such as peptides, carbohydrates, and polymers, monoclonal antibodies are most widely investigated for selectively targeting nanoparticulate drug delivery systems to tumors17, 18, 19. "
ABSTRACT: To compare the anti-cancer activity and cellular uptake of curcumin (Cur) delivered by targeted and non-targeted drug delivery systems in multidrug-resistant cervical cancer cells. Cur was entrapped into poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs, the carboxy-terminal of modified pluronic F127 was conjugated to the amino-terminal of anti-P-glycoprotein (P-gp) (Cur-NPs-APgp). The physical properties of the Cur-NPs, including particle size, zeta potential, particle morphology and Cur release kinetics, were investigated. Cellular uptake and specificity of the Cur-NPs and Cur-NPs-APgp were detected in cervical cancer cell lines KB-V1 (higher expression of P-gp) and KB-3-1 (lower expression of P-gp) using fluorescence microscope and flow cytometry, respectively. Cytotoxicity of the Cur-NPs and Cur-NPs-APgp was determined using MTT assay. The particle size of Cur-NPs and Cur-NPs-APgp was 127 and 132 nm, respectively. The entrapment efficiency and actual loading of Cur-NPs-APgp (60% and 5 μg Cur/mg NP) were lower than those of Cur-NPs (99% and 7 μg Cur/mg NP). The specific binding of Cur-NPs-APgp to KB-V1 cells was significantly higher than that to KB-3-1 cells. Cellular uptake of Cur-NPs-APgp into KB-V1 cells was higher, as compared to KB-3-1 cells. However, the cellular uptake of Cur-NPs and Cur-NPs-IgG did not differ between the two types of cells. Besides, the cytotoxicity of Cur-NPs-APgp in KB-V1 cells was higher than those of Cur and Cur-NPs. The results demonstrate that Cur-NPs-APgp targeted to P-gp on the cell surface membrane of KB-V1 cells, thus enhancing the cellular uptake and cytotoxicity of Cur.Acta Pharmacologica Sinica 05/2012; 33(6):823-31. DOI:10.1038/aps.2012.34 · 2.50 Impact Factor