Receptor Mediated Endocytosis and Cytotoxicity of Transferrin-Mitomycin C Conjugate in the HepG2 Cell and Primary Cultured Rat Hepatocyte.

Tanaka, Tetsuro; Fujishima, Yuko; Kaneo, Yoshiharu

doi:10.1248/bpb.24.268

Cited by 16 publications

(13 citation statements)

References 26 publications

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“…Cellular specificity combined with endocytosis ensures that once the nanoparticle reaches its target, it is readily internalized. For this reason, very often the receptor of choice is associated with endocytosis, such as transferrin receptors (Tanaka et al 2001;Iinuma et al 2002), EGF receptors (Kirpotin et al 2006;Zeng et al 2006;Lee et al 2007;Mi et al 2013), albumin receptors (Schmid et al 2007;Kratz 2008), folate receptors (Lee and Low 1994;Pan et al 2002;Zhang et al 2007;Han et al 2009), and LDL receptors (Chnari et al 2006), to name a few.…”

Section: Surface Chemistrymentioning

confidence: 99%

Exploiting Endocytosis for Nanomedicines

Akinc

Battaglia

2013

Cold Spring Harbor Perspectives in Biology

192

169

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In this article, we briefly review the endocytic pathways used by cells, pointing out their defining characteristics and highlighting physical limitations that may direct the internalization of nanoparticles to a subset of these pathways. A more detailed description of these pathways is presented in the literature. We then focus on the endocytosis of nanomedicines and present how various nanomaterial parameters impact these endocytic processes. This topic is an area of active research, motivated by the recognition that an improved understanding of how nanomaterials interact at the molecular, cellular, and whole-organism level will lead to the design of better nanomedicines in the future. Next, we briefly review some of the important nanomedicines already on the market or in clinical development that serve to exemplify how endocytosis can be exploited for medical benefit. Finally, we present some key unanswered questions and remaining challenges to be addressed by the field.

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Section: Surface Chemistrymentioning

confidence: 99%

Exploiting Endocytosis for Nanomedicines

Akinc

Battaglia

2013

Cold Spring Harbor Perspectives in Biology

192

169

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“…To circumvent this barrier, peptides can also mediate the intracellular delivery of drugs via targeting receptors at the cell surface (Table 1). For receptor targeting strategies, including transferrin [38–40], folate [41–48] and epidermal growth factor receptors [49–51], the EPR mediated accumulation of carrier is followed by improved internalization of the carriers into target cells, a mechanism known as receptor-mediated endocytosis (RME). Using RME strategies, tumors can be selectively targeted by increased localization of the carrier to the tumor and also by enhancement of internalization (Fig.…”

Section: Mechanisms Of Peptide-mediated Tumor Targetingmentioning

confidence: 99%

“…Extensive work on transferrin-mediated targeting was done by Tanaka and coworkers [40]. Transferrin undergoes receptor-mediated endocytosis in a broad range of cells; furthermore, when Mitomycin C is conjugated to transferrin, the resulting conjugate demonstrates unaltered receptor binding properties.…”

Section: Mechanisms Of Peptide-mediated Tumor Targetingmentioning

confidence: 99%

Environmentally responsive peptides as anticancer drug carriers☆

Aluri

Janib

MacKay

2009

Advanced Drug Delivery Reviews

104

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The tumor microenvironment provides multiple cues that may be exploited to improve the efficacy of established chemotherapeutics; furthermore, polypeptides are uniquely situated to capitalize on these signals. Peptides provide: 1) a rich repertoire of biologically specific interactions to draw upon; 2) environmentally-responsive phase behaviors, which may be tuned to respond to signatures of disease; 3) opportunities to direct self-assembly; 4) control over routes of biodegradation; 5) the option to seamlessly combine functionalities into a single polymer via a one-step biosynthesis. As development of cancer-targeted nanocarriers expands, peptides provide a unique source of functional units that may target disease. This review explores potential microenvironmental physiology indicative of tumors and peptides that have demonstrated an ability to target and deliver to these signals.

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“…186 Transferrin-mitomycin C (MMC), the chemotherapeutic DNA crosslinking agent, has been demonstrated to be a useful hybrid as a receptor-mediated targeting system. [187][188][189] The Tf-MMC conjugate bound and was internalized into the human hepatoma cell line HepG2 cell, normal cultures rat hepatocyte, human leukemia cell line HL60 cells and Sarcoma 180 cells. The proliferation of the HepG2 and HL60 cells was inhibited by Tf-MMC in vitro.…”

Section: A Transferrin Conjugates In Drug Deliverymentioning

confidence: 99%

Transferrin/transferrin receptor‐mediated drug delivery

Qian

2002

Medicinal Research Reviews

409

247

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Since transferrin was discovered more than half a century ago, a considerable effort has been made towards understanding tranferrin-mediated iron uptake. However, it was not until recently with the identification and characterization of several new genes related to iron homeostasis, such as the hemochromatosis protein HFE and the iron transporter DMT1, that our knowledge has been advanced dramatically. A major pathway for cellular iron uptake is through internalization of the complex of iron-bound transferrin and the transferrin receptor, which is negatively modulated by HFE, a protein related to hereditary hemochromatosis. Iron is released from transferrin as the result of the acidic pH in endosome and then is transported to the cytosol by DMT1. The iron is then utilized as a cofactor by heme and ribonucleotide reductase or stored in ferritin. Apart from iron, many other metal ions of therapeutic and diagnostic interests can also bind to transferrin at the iron sites and their transferrin complexes can be recognized by many cells. Therefore, transferrin has been thought as a "delivery system" for many beneficial and harmful metal ions into the cells. Transferrin has also be widely applied as a targeting ligand in the active targeting of anticancer agents, proteins, and genes to primary proliferating malignant cells that overexpress transferrin receptors. This is achieved by conjugation of transferrin with drugs, proteins, hybride systems with marcomolecules and as liposomal-coated systems. Conjugates of anticancer drugs with transferrin can significantly improve the selectivity and toxicity and overcome drug resistance, thereby leading to a better treatment. The coupling of DNA to transferrin via a polycation such as polylysine or via cationic liposomes can target and transfer of the extrogenous DNA particularly into proliferating cells through receptor-mediated endocytosis. These kinds of non-viral vectors are potential alternatives to viral vectors for gene therapy, if the transfection efficiency can be improved. Moreover, transferrin receptors have shown potentials in delivery of therapeutic drugs or genes into the brain across blood-brain barrier.

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Receptor Mediated Endocytosis and Cytotoxicity of Transferrin-Mitomycin C Conjugate in the HepG2 Cell and Primary Cultured Rat Hepatocyte.

Cited by 16 publications

References 26 publications

Exploiting Endocytosis for Nanomedicines

Exploiting Endocytosis for Nanomedicines

Environmentally responsive peptides as anticancer drug carriers☆

Transferrin/transferrin receptor‐mediated drug delivery

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