Peptide Conjugation: Before or After Nanoparticle Formation?

Valetti, Sabrina; Mura, Simona; Noiray, Magali; Berlier, Gloria; Dosio, Franco; Vergnaud-Gauduchon, Juliette; Desmaële, Didier; Stella, Barbara; Couvreur, Patrick

doi:10.1021/bc5003423

Cited by 36 publications

(39 citation statements)

References 55 publications

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“…In another study, SQ–GEM was decorated with SQ conjugated targeting peptide CKAAN through coprecipitation. 49,103 The nanoassemblies with CKAAN showed a higher specificity in cellular uptake and cytotoxicity in Paca-2 pancreatic cancer cells. 103 In a separate study, a technology called lipocore was developed.…”

Section: Delivery Systems For Lipid–drug Conjugatementioning

confidence: 99%

Lipid–Drug Conjugate for Enhancing Drug Delivery

2017

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Lipid–drug conjugates (LDCs) are drug molecules that have been covalently modified with lipids. The conjugation of lipids to drug molecules increases lipophilicity and also changes other properties of drugs. The conjugates demonstrate several advantages including improved oral bioavailability, improved targeting to the lymphatic system, enhanced tumor targeting, and reduced toxicity. Based on the chemical nature of drugs and lipids, various conjugation strategies and chemical linkers can be utilized to synthesize LDCs. Linkers and/or conjugation methods determine how drugs are released from LDCs and are critical for the optimal performance of LDCs. In this review, different lipids used for preparing LDCs and various conjugation strategies are summarized. Although LDCs can be administered without a delivery carrier, most of them are loaded into appropriate delivery systems. The lipid moiety in the conjugates can significantly enhance drug loading into hydrophobic components of delivery carriers and thus generate formulations with high drug loading and superior stability. Different delivery carriers such as emulsions, liposomes, micelles, lipid nanoparticles, and polymer nanoparticles are also discussed in this review.

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Section: Delivery Systems For Lipid–drug Conjugatementioning

confidence: 99%

Lipid–Drug Conjugate for Enhancing Drug Delivery

2017

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“…In contrast, in the case of ligand-modified liposomes prepared by the postinsertion method, all of the ligands are facing outward from the membrane but ligand-modified micelles also remain in the reaction solution. [21][22][23] Because the modified micelles have the ability to bind to targeting receptors, it is important to determine the purity of the liposomes, and to evaluate the density of surface ligands, [24][25][26][27][28] which serve as an index of the quality of the liposomes. [29][30][31][32] Surface reaction modification can efficiently modify the liposomal surface without micelle contamination, and ensures that the ligands are orientated facing outward from the membrane.…”

Section: -9)mentioning

confidence: 99%

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

Lee

Sato

Hyodo

et al. 2016

Biological & Pharmaceutical Bulletin

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The surface topology of ligands on liposomes is an important factor in active targeting in drug delivery systems. Accurately evaluating the density of anchors and bioactive functional ligands on a liposomal surface is critical for ensuring the efficient delivery of liposomes. For evaluating surface ligand density, it is necessary to clarify that on the ligand-modified liposomal surfaces, some anchors are attached to ligands but some are not. To distinguish between these situations, a key parameter, surface anchor density, was introduced to specify amount of total anchors on the liposomal surface. Second, the parameter reaction yield was introduced to identify the amount of ligand-attached anchors among total anchors, since the conjugation efficiency is not always the same nor 100%. Combining these independent parameters, we derived: incorporation ratio surface anchor density reaction yield. The term incorporation ratio defines the surface ligand density. Since the surface anchor density represents the density of polyethylene glycol (PEG) on the surfaces in most cases, it also determines liposomal function. It is possible to accurately characterize various PEG and ligand densities and to define the surface topologies. In conclusion, this quantitative methodology can standardize the liposome preparation process and qualify the modified liposomal surfaces.Key words active targeting; surface ligand density; incorporation ratio; surface anchor density; reaction yield; surface topology Nanotechnology has the capability to deliver drugs to specific cell types, but it is important to maximize therapeutic effects and minimize unexpected adverse effects, for this technology to be effectively used.1-4) In using nanoparticles for specific drug delivery, they need to have both a stealth function to prevent non-specific recognition by the reticuloendothelial system (RES), 5,6) and an active targeting function to allow them to bind to the specific cell type of interest. 7-9)Polyethylene glycol (PEG) modification is frequently used to confer a stealth function to nanoparticles. 5,6,10) For active targeting, specific ligands for bioactive molecules such as nucleic acids, peptides, proteins, and antibodies are attached to the surface of nanoparticles via a PEG spacer.11) Many attempts have been made to develop various types of specific ligands for use in active targeting, which is critical for targeting non-fenestrated tissues such as the brain, lung and related tissues. [12][13][14] The procedures used to prepare ligands that are used in modifying nanoparticles are relatively complicated because this increases the number of steps in the preparation process that can lead to conditions where ligand molecules can be unstable.15) Therefore, optimal reaction (modification) conditions and methods for quantifying the density of the attached ligand that is attached to the nanoparticles need to be evaluated precisely.Problems are usually encountered in evaluating both the density of the liposomal ligands and the PEG, since a variety of m...

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“…SQGem NPs have been decorated with the CKAAKN peptide for selective targeting of pancreatic cancer cells. 167 In vivo studies on RipTag2 mice, a model of spontaneously arising islet cell carcinoma, revealed the superior efficacy of the peptidedecorated nanoparticles compared with their non-functionalized counterpart. 168 Altogether, these data clearly demonstrated that the squalenoylation approach is a powerful tool for overcoming the impaired uptake of gemcitabine caused by NT-mediated resistance.…”

Section: Impaired Drug Uptakementioning

confidence: 99%

How can nanomedicines overcome cellular-based anticancer drug resistance?

2016

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Despite the great progress in the field of cancer research, complete remission of cancer patients is a rarely seen outcome in clinics. The failure of a plethora of promising anticancer drugs is mostly due to the insurgence of multidrug resistance (MDR) phenomena with various factors, both physio-pathological and cellular, being responsible for their development. Over the past 40 years, the impressive progress in the nanotechnology field and its application in medicine (i.e., nanomedicine) enabled the development of novel cancer treatments with improved specificity and efficacy, mainly referring to the possibility to overcome MDR. However, the emergence of many nanomedicines defined in the literature as ''overcoming the resistance'' has resulted in very few of them eventually being approved for clinical application and reaching the marketplace (liposomal formulation of doxorubicin (Myocet s , Caelix s ) and paclitaxel nanoparticles (Abraxane s ), for instance). The capacity of nanomedicines to overcome physio-pathologicalbased resistance by enhancing drug accumulation at the tumor site via passive and ligand-mediated targeting has been largely reviewed in the past few years. This review will specifically focus on the cellular mechanisms involved in the MDR, which will be discussed with respect to the cellular site in which their action is exerted (that is, membrane, cytoplasm or nucleus). A complete overview of various nanomedicines designed to bypass or directly inhibit each of these specific resistance mechanisms will be offered.

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Peptide Conjugation: Before or After Nanoparticle Formation?

Cited by 36 publications

References 55 publications

Lipid–Drug Conjugate for Enhancing Drug Delivery

Lipid–Drug Conjugate for Enhancing Drug Delivery

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

How can nanomedicines overcome cellular-based anticancer drug resistance?

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