Development of ligand-targeted liposomes for cancer therapy

University of California, San Francisco, San Francisco, California, United States
Expert Opinion on Therapeutic Targets (Impact Factor: 5.14). 09/2004; 8(4):335-53. DOI: 10.1517/14728222.8.4.335
Source: PubMed


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.

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    • "It is commonly believed that efficiency of nanomedicines can be significantly increased by their ligand-mediated targeting (LMT) to cancer cells. While the potential benefit of LMT was shown in numerous experiments with animals [4] [5] [6] [7], this technology has not made a significant clinical impact on cancer treatment [8] [9]. "
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    ABSTRACT: Nanoencapsulation of anticancer drugs improves their therapeutic indices by virtue of the enhanced permeation and retention effect which achieves passive targeting of nanoparticles in tumors. This effect can be significantly enhanced by active targeting of nanovehicles to tumors. Numerous ligands have been proposed and used in various studies with peptides being considered attractive alternatives to antibodies. This is further reinforced by the availability of peptide phage display libraries which offer an unlimited reservoir of target-specific probes. In particular landscape phages with multivalent display of target-specific peptides which enable the phage particle itself to become a nanoplatform creates a paradigm for high throughput selection of nanoprobes setting the stage for personalized cancer management. Despite its promise, this conjugate of combinatorial chemistry and nanotechnology has not made a significant clinical impact in cancer management due to a lack of using robust processes that facilitate scale-up and manufacturing. To this end we proposed the use of phage fusion protein as the navigating modules of novel targeted nanomedicine platforms which are described in this review.
    FEBS letters 11/2013; 588(2). DOI:10.1016/j.febslet.2013.11.011 · 3.17 Impact Factor
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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), "
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    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
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    • "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 [12] [13] [14] [15] [16]. Historically, the first example of an immunoliposome (IL) was prepared by Torchilin and used to localize in acute canine myocardial infarction [17]. "
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    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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