Peptide–Drug Conjugate Linked via a Disulfide Bond for Kidney Targeted Drug Delivery

Geng, Qian; Sun, Xun; Gong, Tao; Zhang, Zhirong

doi:10.1021/bc300020f

Cited by 55 publications

(47 citation statements)

References 51 publications

(72 reference statements)

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“…Reduction-responsive drug carriers generally contain a disulfide bond which is reduced to sulfydryl by reducing agent, such as GSH, but maintains stable under normal conditions. The intracellular GSH concentration (2-10 mM) is substantially higher than that in the extracellular environment (2-10 mM), which is the main basis of reduction-responsive drug delivery systems (Geng et al, 2012;Bao et al, 2014). Furthermore, the GSH concentration in tumor tissues is several times higher than that in normal tissues (Kuppusamy et al, 2002), which is more helpful to break the disulfide bond between the drug and its carrier, resulting in more rapid drug release at the tumor site.…”

Section: Introductionmentioning

confidence: 99%

A smart tumor targeting peptide–drug conjugate, pHLIP-SS-DOX: synthesis and cellular uptake on MCF-7 and MCF-7/Adr cells

et al. 2015

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Doxorubicin (DOX) is a potent anticancer drug for the treatment of tumors, but the poor specificity and multi-drug resistance (MDR) on tumor cells have restricted its application. Here, a pH and reduction-responsive peptide-drug conjugate (PDC), pHLIP-SS-DOX, was synthesized to overcome these drawbacks. pH low insertion peptide (pHLIP) is a cell penetrating peptide (CPP) with pH-dependent transmembrane ability. And because of the unique cell membrane insertion pattern, it might reverse the MDR. The cellular uptake study showed that on both drug-sensitive MCF-7 and drug-resistant MCF-7/Adr cells, pHLIP-SS-DOX obviously facilitated the uptake of DOX at pH 6.0 and the uptake level on MCF-7/Adr cells was similar with that on MCF-7 cells, indicating that pHLIP-SS-DOX had the ability to target acidic tumor cells and reverse MDR. In vitro cytotoxicity study mediated by GSH-OEt demonstrated that the cytotoxic effect of pHLIP-SS-DOX was reduction responsive, with obvious cytotoxicity at pH 6.0; while it had poor cytotoxicity at pH 7.4, no matter with or without GSH-OEt pretreatment. This illustrated that pHLIP could deliver DOX into tumor cells with acidic microenvironment specifically and could not deliver drugs into normal cells with neutral microenvironment. In summary, pHLIP-SS-DOX is a promising strategy to target drugs to tumors and provides a possibility to overcome MDR.

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Section: Introductionmentioning

confidence: 99%

A smart tumor targeting peptide–drug conjugate, pHLIP-SS-DOX: synthesis and cellular uptake on MCF-7 and MCF-7/Adr cells

et al. 2015

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“…By employing targeting peptides to nanoparticles, drugs have the potential to reduce side effects and toxicity associated with current therapies for kidney disease, and can generate a higher intrarenal drug concentration compared to that of free drug. 32 Notably, many potential candidates for kidney targeting peptides from phage display technologies have been identified, 33 but relatively few nanoparticle studies for targeted drug delivery applications have been attempted in recent years. We present potential peptides, organized by cell target, that have shown renal specificity and can be used as active targeting ligands for nanomedicine.…”

Section: Peptide Ligandsmentioning

confidence: 99%

“…4A and B). 32 A small molecule drug model captopril (CAP), which acts to reduce glomerular hypertension and renal injury, was coupled to the targeting peptide with a disulfide bond. The bond was demonstrated to be cleavable in the kidney, releasing free CAP into the renal proximal tubule cells.…”

Section: Peptide Ligandsmentioning

confidence: 99%

Peptide and antibody ligands for renal targeting: nanomedicine strategies for kidney disease

2017

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The kidney is one of the body’s main filtration organs, and hence, opportunity exists for designing nanomedicine that can naturally accumulate in the kidneys for renal diseases. In addition to traditional physiochemical properties for kidney accumulation, such as size and charge, synthesized nanoparticles can be conjugated with targeting ligands which further home the nanocarriers to cell types of interest In this review, we highlight key studies that have shown success in utilizing peptide- or antibody-based ligands in nanoparticles to target the glomerulus, podocytes, or renal tubule cells in the kidney. In addition, other ligand candidates which have shown renal affinity, but have not yet been integrated into a nanoparticle are also presented. These studies can provide insight into the design of novel clinical solutions for improved detection, prevention, and treatment of renal diseases using nanomedicine efforts

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“…Overall there was comparably higher uptake of labelled compound by the tumour and the conjugate did not easily break up. [126][127][128][129].…”

Section: G3-c12mentioning

confidence: 99%

Inhibitors of Galectins and Implications for Structure-Based Design of Galectin-Specific Therapeutics

2014

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Galectins are a family of galactoside-specific lectins that are involved in a myriad of metabolic and disease processes. Due to roles in cancer and inflammatory and heart diseases, galectins are attractive targets for drug development. Over the last two decades, various strategies have been used to inhibit galectins, including polysaccharide-based therapeutics, multivalent display of saccharides, peptides, peptidomimetics, and saccharide-modifications. Primarily due to galectin carbohydrate binding sites having high sequence identities, the design and development of selective inhibitors targeting particular galectins, thereby addressing specific disease states, is challenging. Furthermore, the use of different inhibition assays by research groups has hindered systematic assessment of the relative selectivity and affinity of inhibitors. This review summarises the status of current inhibitors, strategies, and novel scaffolds that exploit subtle differences in galectin structures that, in conjunction with increasing available data on multiple galectins, is enabling the feasible design of effective and specific inhibitors of galectins. small-molecule crystallography, University of London, UK) undertook post-doctoral research in protein X-ray crystallography and drug-design in academia and industry within Canada, USA, Switzerland and Australia. In 2002 Helen established a protein X-ray crystallography structural biology group at the Institute for Glycomics, Griffith University. As recognition of her international contribution to structural biology and chemistry she was admitted as fellow of the Royal Society of Chemistry (FRSC) in 2006. Her research involves determination of atomic protein structure, analysis of protein-ligand interactions and application of this information in understanding protein function and for structure based drug-design. Her research group has a major focus on lectins critical to disease progression including her research program on galectins that have importance in serious conditions including cancer. Khuchtumur Bum-Erdene completed his Bachelors degree in Chemistry (

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Peptide–Drug Conjugate Linked via a Disulfide Bond for Kidney Targeted Drug Delivery

Cited by 55 publications

References 51 publications

A smart tumor targeting peptide–drug conjugate, pHLIP-SS-DOX: synthesis and cellular uptake on MCF-7 and MCF-7/Adr cells

A smart tumor targeting peptide–drug conjugate, pHLIP-SS-DOX: synthesis and cellular uptake on MCF-7 and MCF-7/Adr cells

Peptide and antibody ligands for renal targeting: nanomedicine strategies for kidney disease

Inhibitors of Galectins and Implications for Structure-Based Design of Galectin-Specific Therapeutics

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