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: Rauzah Hashim[Show abstract] [Hide abstract]
ABSTRACT: Vesicles formed by self-assembly of lipids and surfactants are increasingly recognised as carriers for drug delivery applications in disease targeting and many other biomedical-related areas, demonstrable by the growing number of significant publications. This manuscript reviews important facets of lipid-based vesicles as drug carriers and their surface modification to achieve controlled release and selective cell targeting. We cover both the more commonly used ionic phospholipid vesicle carriers and the rapidly growing field of non-ionic vesicles/niosomes using self-assembly of uncharged amphiphilic molecules, which could be formed using sugar surfactants or glycolipids, sorbitan esters, and polyoxyethylene alkyl ethers. Due to their lower cost, biodegradability, low-toxicity, low-immunogenicity, and specific sugar-cell recognition, much attention would be devoted to glycolipid bio-surfactants as potential carriers for targeted delivery. Specifically, our review points to the design consideration of lipid and surfactant nano-carriers based on critical packing parameter, membrane curvature, and the effects of hydrophobic chain structures. We also dedicate a section of this review to summarise some novel application of various lipid liquid crystal phases in drug delivery, and how in turn these are related to chemical structures of the lipid entities. The final section of this review outlines the application of lipid vesicles as delivery agents for diagnostic imaging.Medicinal Chemistry Communication 11/2014; 5(11):1602-1618. DOI:10.1039/C4MD00085D · 2.63 Impact Factor
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ABSTRACT: The detection of circulating tumor cells (CTCs) in the blood of patients with cancer is crucial for early diagnosis of cancer, cancer prognosis, assessment of tumor sensitivity to anticancer drugs and personalization of anticancer therapy. Here we report new surface-enhanced Raman scattering (SERS) nanoparticles for direct detection of CTCs in the blood. Under the optimized experimental conditions, our SERS nanoparticles exhibit satisfying performances for direct detection of cancer cells in the rabbit blood. A good linear relationship is obtained between the SERS intensity and the concentration of cancer cells in the range of 5-500 cells/mL (R2 = 0.9935). The strong linear relationship indicates that our SERS nanoparticles can be used for the quantitative analysis of cancer cells in the blood and the limit of detection (LOD) is 5 cells/mL, which is lowest compared with the reported values. The SERS nanoparticles also have an excellent specificity for detection of cancer cells in the rabbit blood. The above results reinforce that our SERS nanoparticles can be used for direct detection of CTCs in the blood with excellent specificity and high sensitivity.ACS Applied Materials & Interfaces 04/2015; 7(18):9965-9971. DOI:10.1021/acsami.5b02276 · 5.90 Impact Factor
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ABSTRACT: To minimize the systemic toxicity prevalent to chemotherapeutics, we designed a novel anticancer drug-encapsulating liposome conjugated with an RNA aptamer specific to the prostate specific membrane antigen (PSMA), which is expressed on the surface of prostate cancer cells. The RNA aptamer-conjugated liposome, termed an aptamosome, was prepared by the post-insertion method, in which RNA aptamer-conjugated micelles were inserted into a liposome. These nanosized (90–100 nm) aptamer-conjugated liposomes specifically bind to LNCaP prostate epithelial cells that express PSMA and thus cause the nanoparticles to have significantly enhanced in vitro cellular binding and uptake as compared with nontargeted nanoparticles that lack the PSMA aptamer. Aptamosomes encapsulated with the anticancer drug doxorubicin (Dox) were significantly more toxic to the targeted LNCaP cells than to nontargeted cancer cells. Dox-encapsulating aptamosomes administered to LNCaP xenograft nude mice were selectively retained in tumor tissue. We also demonstrated in vivo anticancer efficacy of the Dox-encapsulating PSMA-aptamosomes on tumor size regression in LNCaP xenograft mice. We suggest that the encapsulation of toxic chemicals with aptamer-conjugated liposomes will enable the use of these bioconjugates in clinical practice with fewer side effects.Journal of Controlled Release 12/2014; 196. DOI:10.1016/j.jconrel.2014.10.018 · 7.26 Impact Factor