Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery

Lo, Albert; Lin, Chin‐Tarng; Wu, Han-Chung

doi:10.1158/1535-7163.mct-07-2359

Cited by 162 publications

(142 citation statements)

References 36 publications

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“…The candidate tumor-homing phage clones were randomly selected and identified by in vivo homing experiments. DNA sequences of the selected phages and targeting peptide synthesis were described in our previous reports (20,22).…”

Section: Methodsmentioning

confidence: 99%

Antiangiogenic Targeting Liposomes Increase Therapeutic Efficacy for Solid Tumors

Chang

Chiu

Kuo

et al. 2009

Journal of Biological Chemistry

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It is known that solid tumors recruit new blood vessels to support tumor growth, but the molecular diversity of receptors in tumor angiogenic vessels might also be used clinically to develop better targeted therapy. In vivo phage display was used to identify peptides that specifically target tumor blood vessels. Several novel peptides were identified as being able to recognize tumor vasculature but not normal blood vessels in severe combined immunodeficiency (SCID) mice bearing human tumors. These tumor-homing peptides also bound to blood vessels in surgical specimens of various human cancers. The peptidelinked liposomes containing fluorescent substance were capable of translocating across the plasma membrane through endocytosis. With the conjugation of peptides and liposomal doxorubicin, the targeted drug delivery systems enhanced the therapeutic efficacy of the chemotherapeutic agent against human cancer xenografts by decreasing tumor angiogenesis and increasing cancer cell apoptosis. Furthermore, the peptide-mediated targeting liposomes improved the pharmacokinetics and pharmacodynamics of the drug they delivered compared with nontargeting liposomes or free drugs. Our results indicate that the tumor-homing peptides can be used specifically target tumor vasculature and have the potential to improve the systemic treatment of patients with solid tumors.

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Section: Methodsmentioning

confidence: 99%

Antiangiogenic Targeting Liposomes Increase Therapeutic Efficacy for Solid Tumors

Chang

Chiu

Kuo

et al. 2009

Journal of Biological Chemistry

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“…A prominent example of a PEGylated nanoparticle is PEG-liposomal doxorubicin (Lipo-Dox), which has been approved by the Food and Drug Administration for clinical treatment of ovarian and breast carcinomas and Kaposi's sarcoma (6,7). Tumor-binding ligands such as peptides (8,9) and antibodies (10,11) may be conjugated to the distal terminus of PEGylated nanoparticles and macromolecules to increase targeting specificity. Thus far, various tumor-associated antigens or receptors have been validated as targets for PEGylated compounds, especially for immunoliposomes (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Endocytosis of PEGylated Agents Enhances Cancer Imaging and Anticancer Efficacy

Chuang

Wang

Chen

et al. 2010

Molecular Cancer Therapeutics

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PEGylated nanoparticles and macromolecules are increasingly used in cancer imaging and anticancer treatment. The role of receptor-mediated endocytosis in the efficacy of these agents, however, has not been clearly defined. Here, we developed a matched pair of endocytic and nonendocytic receptors to directly and unambiguously assess this issue. The ligand-binding domains of the low-density lipoprotein receptor (LDLR) or a truncated LDLR lacking the NPXY endocytosis motif (ΔLDLR) were replaced with an anti-polyethylene glycol antibody (αPEG) to form endocytic αPEG-LDLR and nonendocytic αPEG-ΔLDLR receptors. The receptors were stably expressed at similar levels on the surface of HCC36 cells. HCC36/αPEG-LDLR cells, but not HCC36/αPEG-ΔLDLR cells, rapidly endocytosed PEG-quantum dots and PEG-liposomal doxorubicin (LipoDox) in vitro and in vivo. Lipo-Dox was significantly more cytotoxic to HCC36/αPEG-LDLR cells than to HCC36/αPEG-ΔLDLR cells. HCC36/αPEG-LDLR tumors also accumulated significantly more PEGylated near-IR probes (PEG-NIR797) and In than HCC36/αPEG-ΔLDLR tumors in vivo. Furthermore, Lipo-Dox more significantly suppressed the growth of established HCC36/αPEG-LDLR tumors as compared with HCC36/αPEG-ΔLDLR tumors. Our data show that endocytosis of PEGylated probes and drugs enhances both cancer imaging and anticancer efficacy, indicating that endocytic receptors are superior targets for the design of cancer imaging probes and immunoliposomal drugs. Mol Cancer Ther; 9(6); 1903-12.

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“…187 Lo et al 187 synthesized a targeted drug delivery system by coupling SP94 with PEGylated liposomal DOX (SP94-LD). Studies that they implemented on mice bearing HCC xenografts confirmed the targeting efficiency of SP94 and demonstrated the superior targeting ability of SP94 over the phage clone PC94 and the enhanced therapeutic effect of SP94-LD compared with control peptide conjugated LD (CP-LD) and LD.…”

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confidence: 99%

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

Li¹,

Zhang²,

Wang³

et al. 2016

IJN

117

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Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery

Abstract: Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide.

Cited by 162 publications

References 36 publications

Antiangiogenic Targeting Liposomes Increase Therapeutic Efficacy for Solid Tumors

Antiangiogenic Targeting Liposomes Increase Therapeutic Efficacy for Solid Tumors

Endocytosis of PEGylated Agents Enhances Cancer Imaging and Anticancer Efficacy

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

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