Peptide‐mediated cancer targeting of nanoconjugates

Raha, Sumita; Paunesku, Tatjana; Woloschak, Gayle E.

doi:10.1002/wnan.121

Cited by 60 publications

(53 citation statements)

References 63 publications

(117 reference statements)

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“…RGD peptides conjugated with different cytostatic agents are likely to exhibit an antitumour and antiangiogenic synergetic effect. During the last few years, a number of RGD-cytotoxic drugs were developed and showed promising activities in vitro and in vivo [15,16].…”

Section: Introductionmentioning

confidence: 99%

In vitro assessment of the cytotoxic effects of novel RGD analogues

Balacheva¹,

Илиев²,

Detcheva³

et al. 2012

Biodiscovery

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The RGD sequence is present in many extracellular matrix proteins and intracellular proteins, including caspases. Synthetic RGD peptides may affect adhesion, migration and tumour metastasis, or directly induce apoptosis. Several RGD peptides were synthesized, and their anti-adhesive and cytotoxic properties were analyzed in vitro.Here we present the cytotoxic activities of RGD, R(NO 2 )GD, CavGD and RGD-OMe on non-tumour 3T3 cells and tumour cell lines HepG2 and MCF-7. The cell growth inhibitory effects of RGD-OMe are significantly higher than those of RGD on the cell lines used. Evidently the modification in the carboxylic group of RGD with simple esterification increases the cell growth inhibitory effects of the parent compound.

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Section: Introductionmentioning

confidence: 99%

In vitro assessment of the cytotoxic effects of novel RGD analogues

Balacheva¹,

Илиев²,

Detcheva³

et al. 2012

Biodiscovery

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“…Due to their small size, peptides are also ideal for multiple modifications of nanoparticle constructs and generation of pluripotent nanoparticles. 38 Moreover, α-MSH binds to melanocortin receptors and, in particular, is a potent agonist of the melanocortin type 1 receptor (MCR1, overexpressed by many melanoma cells 39 ) and binds to MCR1 with high affinity (IC 50 0.21 nmol/L). 40 Importantly, more than 80% of human metastatic melanoma samples have been found to display MCR1.…”

Section: Resultsmentioning

confidence: 99%

Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles

Vannucci¹,

Falvo²,

Fornara³

et al. 2012

IJN

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Background: Nanoparticle-based systems are promising for the development of imaging and therapeutic agents. The main advantage of nanoparticles over traditional systems lies in the possibility of loading multiple functionalities onto a single molecule, which are useful for therapeutic and/or diagnostic purposes. These functionalities include targeting moieties which are able to recognize receptors overexpressed by specific cells and tissues. However, targeted delivery of nanoparticles requires an accurate system design. We present here a rationally designed, genetically engineered, and chemically modified protein-based nanoplatform for cell/tissue-specific targeting. Methods: Our nanoparticle constructs were based on the heavy chain of the human protein ferritin (HFt), a highly symmetrical assembly of 24 subunits enclosing a hollow cavity. HFt-based nanoparticles were produced using both genetic engineering and chemical functionalization methods to impart several functionalities, ie, the α-melanocyte-stimulating hormone peptide as a melanoma-targeting moiety, stabilizing and HFt-masking polyethylene glycol molecules, rhodamine fluorophores, and magnetic resonance imaging agents. The constructs produced were extensively characterized by a number of physicochemical techniques, and assayed for selective melanoma-targeting in vitro and in vivo. Results: Our HFt-based nanoparticle constructs functionalized with the α-melanocytestimulating hormone peptide moiety and polyethylene glycol molecules were specifically taken up by melanoma cells but not by other cancer cell types in vitro. Moreover, experiments in melanoma-bearing mice indicate that these constructs have an excellent tumor-targeting profile and a long circulation time in vivo. Conclusion: By masking human HFt with polyethylene glycol and targeting it with an α-melanocyte-stimulating hormone peptide, we developed an HFt-based melanoma-targeting nanoplatform for application in melanoma diagnosis and treatment. These results could be of general interest, because the same strategy can be exploited to develop ad hoc nanoplatforms for specific delivery towards any cell/tissue type for which a suitable targeting moiety is available. Keywords: multifunctional nanoparticles, ferritin, nanoplatform, cancer-targeting, melanoma IntroductionDevelopment of multifunctional nanoparticles for nanomedicine applications, such as cell/tissue-specific delivery, biomedical imaging and therapy, has recently gained wide popularity. [1][2][3][4] Various types of materials, including synthetic polymers and lipids, have been increasingly utilized as platforms for nanoparticle synthesis. 1,5 Despite the large number of bioconjugation techniques available, the attainment of multifunctional nanoprobes endowed with desired bioactivity, targeting specificity, and stability remains a challenge. Approaches using protein-cage structures, such as proteins belonging to the ferritin family, are novel and very promising. 6,7 Apoferritin is a highly symmetrical multimeric protein consisting of 2...

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“…CPPs and ACPPs for the preparation of nanoparticles designed for cancer research have been described in a recent review [77]. Dendrimer nanoparticles coated with ACPPs have been labeled with both Cy5 and gadolinium, and used as a dual probe for magnetic resonance imaging and in vivo fluorescence in clinical detection and staging of tumors, providing a correlation between tomographic imaging, which can detect a wide variety of tumors from different anatomical sites, and high but superficial resolution imaging, which is effective for intraoperative surgical guidance [78].…”

Section: Antimicrobial and Cell-penetrating Peptidesmentioning

confidence: 99%

Short peptides as biosensor transducers

2011

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This review deals with short peptides (up to 50 amino acids) as biomimetic active recognition elements in sensing systems. Peptide-based sensors have been developed in recent years according to different strategies. Synthetic peptides have been designed on the basis of known interactions between single or a few amino acids and targets, with attention being paid to the presence of peptide motifs known to allow intermolecular self-organization of the sensing peptides over the sensor surface. Sensitive and sophisticated sensors have been obtained in this way, but the use of designed peptides is limited by severe difficulties in their in silico design. Short peptides from random phage display have been selected in a random way from large, unfocussed, and often preexisting and commercially available phage display libraries, with no design elements. Such peptides often perform better than antibodies, but they are difficult to select when the target is a small molecule because of the need to immobilize it with considerable modifications of its structure. Artificial, miniaturized receptors have been obtained from the reduction of the known sequence of a natural receptor down to a synthesizable and yet stable one. Alternatively, binding sites have been created over a designed, stable peptide scaffold. Short peptides have also been used as active elements for the detection of their own natural receptors: pathogenic bacteria have been detected with antimicrobial and cell-penetrating peptides, but key challenges such as detection of bacteria in real samples, improved sensitivity, and improved selectivity have to be faced. Peptide substrates have been conjugated to fluorescent quantum dots to obtain disposable sensors for protease activity with high sensitivity. Ferrocene-peptide conjugates have been used for electrochemical sensing of protease activity.

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Peptide‐mediated cancer targeting of nanoconjugates

Cited by 60 publications

References 63 publications

In vitro assessment of the cytotoxic effects of novel RGD analogues

In vitro assessment of the cytotoxic effects of novel RGD analogues

Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles

Short peptides as biosensor transducers

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