Thermoresponsive and biodegradable linear-dendritic nanoparticles for targeted and sustained release of a pro-apoptotic drug

Stöver, T.; Kim, Young S.; Lowe, Timothy J.; Kester, Mark

doi:10.1016/j.biomaterials.2007.09.037

Cited by 95 publications

(67 citation statements)

References 32 publications

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“…Exploration of PNIPAAM moieties for targeted delivery offers the advantages of good sensitivity, reversible transitions and low cytotoxicity when compared with many cationic polymers. Drug release can be readily tuned to vary with pH and temperature [158,159]. The degradation of these polymers can be altered by changing the hydrophilicity through alteration of the chemical structure of the PNI-PAAM.…”

Section: Growth Factor Release On Demandmentioning

confidence: 99%

Growth factor delivery-based tissue engineering: general approaches and a review of recent developments

Lee

Silva

Mooney

2010

J. R. Soc. Interface.

1,203

952

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The identification and production of recombinant morphogens and growth factors that play key roles in tissue regeneration have generated much enthusiasm and numerous clinical trials, but the results of many of these trials have been largely disappointing. Interestingly, the trials that have shown benefit all contain a common denominator, the presence of a material carrier, suggesting strongly that spatio-temporal control over the location and bioactivity of factors after introduction into the body is crucial to achieve tangible therapeutic effect. Sophisticated materials systems that regulate the biological presentation of growth factors represent an attractive new generation of therapeutic agents for the treatment of a wide variety of diseases. This review provides an overview of growth factor delivery in tissue engineering. Certain fundamental issues and design strategies relevant to the material carriers that are being actively pursued to address specific technical objectives are discussed. Recent progress highlights the importance of materials science and engineering in growth factor delivery approaches to regenerative medicine.

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Section: Growth Factor Release On Demandmentioning

confidence: 99%

Growth factor delivery-based tissue engineering: general approaches and a review of recent developments

Lee

Silva

Mooney

2010

J. R. Soc. Interface.

1,203

952

View full text Add to dashboard Cite

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“…Ceramide itself is rather difficult to use as a drug because of its poor water solubility and rapid physiological degradation. However, recent attempts to deliver ceramide in liposomes or nanovesicles may allow for new therapeutic strategies [212,213]. In addition, water-soluble analogues of ceramide may play an important role in eliminating cancer cells or replacing ceramide when it is needed [79,214].…”

Section: Sphingolipid Biosynthesis In the Endoplasmic Reticulum: Enzymentioning

confidence: 99%

Ceramide signaling in cancer and stem cells

Bieberich

2008

Future Lipidology

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Most of the previous work on the sphingolipid ceramide has been devoted to its function as an apoptosis inducer. Recent studies, however, have shown that in stem cells, ceramide has additional nonapoptotic functions. In this article, ceramide signaling will be reviewed in light of 'systems interface biology': as an interconnection of sphingolipid metabolism, membrane biophysics and cell signaling. The focus will be on the metabolic interconversion of ceramide and sphingomyelin or sphingosine-1-phosphate. Lipid rafts and sphingolipid-induced protein scaffolds will be discussed as a membrane interface for lipid-controlled cell signaling. Ceramide/sphingomyelin and ceramide/ sphingosine-1-phosphate-interdependent cell-signaling pathways are significant for the regulation of cell polarity, apoptosis and/or proliferation, and as novel pharmacologic targets in cancer and stem cells. Keywordsapoptosis; cancer; cell polarity; ceramide; ES cells; lipid rafts; sphingomyelin; sphingosine-1-phosphate Ceramide & its derivatives: from metabolism to cell signalingThe structural core of ceramide is the sphingoid base sphingosine (Figure 1), a lipid that is synthesized from the amino acid serine and the activated fatty acid palmitoyl-CoA (Figure 2). Sphingosine (or sphingenine) was first isolated and characterized by the German pathologist and 'father of neurochemistry ' Johann Ludwig Wilhelm Thudichum (1829-1901 [1,2]. He coined the term sphingolipids, which is derived from 'sphingos', the genitive of Sphinx. In Greek, 'sphingo' means 'to strangle'. According to the legend, a fate of death was meant for everyone who could not solve the riddles posed by the Sphinx. Quite ironically, this is how many sphingolipid researchers may feel when faced with analyzing the function of ceramide. The riddle of ceramide, its function and how it acts as signaling lipid, is far from being solved. To ease our fears when confronted with the Sphinx in sphingolipid biochemistry, a related Greek word, 'sphingein', meaning 'to bind tight', alludes to the possibility of solving the enigma of ceramide by identifying its binding proteins.In addition to ceramide, more than a hundred different sphingolipids are known. The most comprehensive collection of sphingolipids, with respect to their characteristics and structures, can be found at [401], a Webpage supported by the National Institutes of General Medical Sciences [3,4]. Sphingolipids are essential components of cellular membranes and have been (Figure 3) . Among these, their roles as pro-or anti-apoptotic and pro-or anti-proliferative signaling lipids are the most important. Most recently, our group has found that establishment of cell polarity during embryonic development is another biological process regulated by sphingolipids [28]. To define a profile of functions for individual sphingolipids is difficult because of their rapid metabolic interconversion. To add to this predicament, several derivatives of ceramide have functions similar to ceramide itself. Hence, novel techniques are need...

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“…The glycosphingolipid translocase properties of P-gp and other ABC proteins (22)(23)(24) prompted our investigation of glycolipid synthesis in cells challenged with short-chain ceramide analogs, as these cell-permeable agents have been used extensively in studies on ceramide cytotoxicity and are candidates for clinical study (41,42). Although multidrugresistant cancer cells expressing high levels of P-gp have been employed in the majority of studies (14,15,21,43,44), the present study marks the first time that the role of P-gp in ceramide metabolism and cytotoxicity has been evaluated by using cells with conditional expression of P-gp.…”

Section: Discussionmentioning

confidence: 99%

Expression of P-glycoprotein in HeLa cells confers resistance to ceramide cytotoxicity

Chapman

Gouazé-Andersson²,

Cabot³

2010

Int J Oncol

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Abstract. The role of glucosylceramide synthase (GCS) in regulating ceramide-induced apoptosis has been widely studied. The purpose of this investigation was to evaluate the role of P-glycoprotein (P-gp) in regulating ceramide cytotoxicity by using C 6 -ceramide. To accomplish this, we employed HeLa cells with conditional expression of the multidrug resistance gene 1/P-gp. HeLa cells expressing P-gp (P-gp/on cells) challenged with [14 C]C 6 -ceramide (6 μM), synthesized 4.5-fold the amount of C 6 -glucosylceramide (GC) compared to HeLa cells with suppressed expression of P-gp (P-gp/off cells), whereas the generated levels of C 6 -sphingomyelin were almost equal (33 and 29% of intracellular 14 C, respectively). Tamoxifen, a P-gp antagonist, decreased the C 6 -GC levels from 3.5-1.0% in the P-gp/off and from 17-2.8% of the total lipid 14 C levels in the P-gp/on cells. Tamoxifen did not inhibit cell-free C 6 -GC synthesis in the P-gp/off or P-gp/on homogenates. However, a specific GCS inhibitor, ethylenedioxy-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (ethylenedioxy-P4), blocked synthesis by 90%. In the cytotoxicity assays, the P-gp/off cells were sensitive to C 6 -ceramide and the P-gp/on cells were resistant. Resistance to C 6 -ceramide in the P-gp/on cells was reversed by tamoxifen but not by ethylenedioxy-P4. Experiments in another cervical cancer model showed that multidrug-resistant P-gp-rich KB-V1 cells synthesized 3-fold more C 6 -GC from C 6 -ceramide than the parental, P-gp-poor KB-3-1 cells, and whereas tamoxifen had no effect on the C 6 -GC synthesis in the KB-3-1 cells, it inhibited synthesis by 70% in the KB-V1 cells. This study demonstrates that P-gp potentiates C 6 -ceramide glycosylation and if antagonized augments C 6 -ceramide sensitivity, both features previously ascribed to GCS. We propose that P-gp can be an effective target for enhancing short-chain ceramide cytotoxicity in the treatment of drug-resistant cancer.

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Thermoresponsive and biodegradable linear-dendritic nanoparticles for targeted and sustained release of a pro-apoptotic drug

Cited by 95 publications

References 32 publications

Growth factor delivery-based tissue engineering: general approaches and a review of recent developments

Growth factor delivery-based tissue engineering: general approaches and a review of recent developments

Ceramide signaling in cancer and stem cells

Expression of P-glycoprotein in HeLa cells confers resistance to ceramide cytotoxicity

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