Article
A novel peptide specifically binding to nasopharyngeal carcinoma for targeted drug delivery.
Institute of Pathology and Graduate Institute of Oral Biology, College of Medicine, National Taiwan University, Taipei.
Cancer Research (impact factor:
7.86).
12/2004;
64(21):8002-8.
DOI:10.1158/0008-5472.CAN-04-1948
pp.8002-8
Source: PubMed
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Citations (0)
- Cited In (5)
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Article: A novel peptide enhances therapeutic efficacy of liposomal anti-cancer drugs in mice models of human lung cancer.
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ABSTRACT: Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy.PLoS ONE 02/2009; 4(1):e4171. · 4.09 Impact Factor -
Article: Peptide-mediated liposomal drug delivery system targeting tumor blood vessels in anticancer therapy.
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ABSTRACT: Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.Journal of Oncology 01/2010; 2010:723798. -
Article: Single chain anti-c-Met antibody conjugated nanoparticles for in vivo tumor-targeted imaging and drug delivery.
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ABSTRACT: Aberrantly expressed c-Met, the receptor for hepatocyte growth factor (HGF), has been implicated in human lung cancer as well as malignancy, metastasis and drug-resistance in other human cancers. Thus, this molecule could be a potential target for antibody-based cancer therapy. Targeting delivery of compound to tumor represented benefit for cancer detection and therapy. In this study, we utilized phage display to identify human single chain variable fragment (scFv) antibodies that specifically bound to c-Met protein. The anti-c-Met scFvs selectively bound to and internalized in several lung cancer cell lines expressing c-Met. Conjugation of anti-c-Met scFv with PEGylated liposomes enabled the efficient delivery of doxorubicin into cancer cells where it exerted cytotoxic activity by inducing apoptosis pathway. In addition, in vivo fluorescent imaging by scFv-conjugated quantum dots showed higher tumor uptake and increased tumor-normal tissue ratios. In a tumor xenograft model, anti-c-Met immunoliposome was found to selectively increase tumor accumulation of a chemotherapeutic drug and enhance its antitumor activity. Taken together, our results suggest that anti-c-Met scFv-mediated drug delivery systems show great promise in tumor-targeted therapy and imaging.Biomaterials 02/2011; 32(12):3265-74. · 7.40 Impact Factor
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Keywords
5-year survival rate
advanced cases
common cancer
drug delivery
fluorescent substance
good candidate
L-peptide-linked liposomes
L-peptide-Lipo-Dox
L-peptide-Lipo-Dox suppressed tumor growth
Nasopharyngeal carcinoma
normal nasal mucosal cells
novel L-peptide
NPC cell lines
NPC cells
NPC solid tumors
random peptide library
SCID mice bearing NPC xenografts
southern China
synthetic L-peptide
tumor cell surfaces