Nanocarrier

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 49917 Experts worldwide ranked by ideXlab platform

Frederik R. Wurm - One of the best experts on this subject based on the ideXlab platform.

  • Noncovalent Targeting of Nanocarriers to Immune Cells with Polyphosphoester‐Based Surfactants in Human Blood Plasma
    Advanced science (Weinheim Baden-Wurttemberg Germany), 2019
    Co-Authors: Johanna Simon, Volker Mailander, Katharina Landfester, Kristin N. Bauer, Jens Langhanki, Till Opatz, Frederik R. Wurm
    Abstract:

    Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T-cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the Nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to Nanocarriers requires new chemistry for each Nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the Nanocarriers' surface resulting in specific uptake into DCs combined with low protein adsorption of PPEs is presented. PPEs with hydrophobic anchors and multiple mannose units are reported and adsorbed to different model Nanocarriers. Their protein corona remain similar to pure stealth Nanocarriers and prove only low uptake into nontargeted cells (monocytes). Due to the "stealth" properties of PPEs, a high specific uptake into DCs is achieved after incubation in human blood plasma, proving an efficient combination of "stealth" and targeting after simple adsorption of the PPEs. This strategy can transform any Nanocarrier into DC-targeting by noncovalent adsorption of PPEs and will aid in developing novel immunotherapies.

  • noncovalent targeting of Nanocarriers to immune cells with polyphosphoester based surfactants in human blood plasma
    Advanced Science, 2019
    Co-Authors: Johanna Simon, Volker Mailander, Katharina Landfester, Kristin N. Bauer, Jens Langhanki, Till Opatz, Frederik R. Wurm
    Abstract:

    Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T-cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the Nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to Nanocarriers requires new chemistry for each Nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the Nanocarriers' surface resulting in specific uptake into DCs combined with low protein adsorption of PPEs is presented. PPEs with hydrophobic anchors and multiple mannose units are reported and adsorbed to different model Nanocarriers. Their protein corona remain similar to pure stealth Nanocarriers and prove only low uptake into nontargeted cells (monocytes). Due to the "stealth" properties of PPEs, a high specific uptake into DCs is achieved after incubation in human blood plasma, proving an efficient combination of "stealth" and targeting after simple adsorption of the PPEs. This strategy can transform any Nanocarrier into DC-targeting by noncovalent adsorption of PPEs and will aid in developing novel immunotherapies.

  • Phosphonylation Controls the Protein Corona of Multifunctional Polyglycerol-Modified Nanocarriers.
    Macromolecular bioscience, 2019
    Co-Authors: Ann Kathrin Danner, Volker Mailander, Svenja Morsbach, Katharina Landfester, Susanne Schöttler, Evandro M. Alexandrino, Sophie Hammer, Holger Frey, Frederik R. Wurm
    Abstract:

    Nanocarriers are a platform for modern drug delivery. In contact with blood, proteins adsorb to Nanocarriers, altering their behavior in vivo. To reduce unspecific protein adsorption and unspecific cellular uptake, Nanocarriers are modified with hydrophilic polymers like poly(ethylene glycol) (PEG). However, with PEG the attachment of further functional structures such as targeting units is limited. A method to introduce multifunctionality via polyglycerol (PG) while maintaining the hydrophilicity of PEG is introduced. Different amounts of negatively charged phosphonate groups (up to 29 mol%) are attached to the multifunctional PGs (Mn 2-4 kg mol-1 , Ð < 1.36) by post-modification. PGs are used in the miniemulsion/solvent evaporation procedure to prepare model Nanocarriers. Their behavior in human blood plasma is investigated to determine the influence of the negative charges on the protein adsorption. The protein corona of PGylated Nanocarriers is similar to PEGylated analogs (on same Nanocarriers), but the protein pattern could be gradually altered by the integration of phosphonates. This is the first report on the gradual increase of negative charges on Nanocarriers and intriguingly up to a certain amount of phosphonate groups per Nanocarrier the protein pattern remains relatively unchanged, which is important for the future design of Nanocarriers.

  • Carbohydrate Nanocarriers in biomedical applications: functionalization and construction.
    Chemical Society reviews, 2015
    Co-Authors: Biao Kang, Katharina Landfester, Till Opatz, Frederik R. Wurm
    Abstract:

    The specific targeting of either tumor cells or immune cells in vivo by carefully designed and appropriately surface-functionalized Nanocarriers may become an effective therapeutic treatment for a variety of diseases. Carbohydrates, which are prominent biomolecules, have shown their outstanding ability in balancing the biocompatibility, stability, biodegradability, and functionality of Nanocarriers. The recent applications of sugar (mono/oligosaccharides and/or polysaccharides) for the development of nanomedicines are summarized in this review, including the application of carbohydrates for the surface-functionalization of various Nanocarriers and for the construction of the Nanocarrier itself. Current problems and challenges are also addressed.

Johanna Simon - One of the best experts on this subject based on the ideXlab platform.

  • brush conformation of polyethylene glycol determines the stealth effect of Nanocarriers in the low protein adsorption regime
    Nano Letters, 2021
    Co-Authors: Shuai Jiang, Johanna Simon, Volker Mailander, David Paslick, Marieluise Frey, Manfred Wagner, Daniel Crespy
    Abstract:

    For Nanocarriers with low protein affinity, we show that the interaction of Nanocarriers with cells is mainly affected by the density, the molecular weight, and the conformation of polyethylene glycol (PEG) chains bound to the Nanocarrier surface. We achieve a reduction of nonspecific uptake of ovalbumin Nanocarriers by dendritic cells using densely packed PEG chains with a "brush" conformation instead of the collapsed "mushroom" conformation. We also control to a minor extent the dysopsonin adsorption by tailoring the conformation of attached PEG on the Nanocarriers. The brush conformation of PEG leads to a stealth behavior of the Nanocarriers with inhibited uptake by phagocytic cells, which is a prerequisite for successful in vivo translation of nanomedicine to achieve long blood circulation and targeted delivery. We can clearly correlate the brush conformation of PEG with inhibited phagocytic uptake of the Nanocarriers. This study shows that, in addition to the surface's chemistry, the conformation of polymers controls cellular interactions of the Nanocarriers.

  • noncovalent targeting of Nanocarriers to immune cells with polyphosphoester based surfactants in human blood plasma
    Advanced Science, 2019
    Co-Authors: Johanna Simon, Volker Mailander, Katharina Landfester, Kristin N. Bauer, Jens Langhanki, Till Opatz, Frederik R. Wurm
    Abstract:

    Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T-cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the Nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to Nanocarriers requires new chemistry for each Nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the Nanocarriers' surface resulting in specific uptake into DCs combined with low protein adsorption of PPEs is presented. PPEs with hydrophobic anchors and multiple mannose units are reported and adsorbed to different model Nanocarriers. Their protein corona remain similar to pure stealth Nanocarriers and prove only low uptake into nontargeted cells (monocytes). Due to the "stealth" properties of PPEs, a high specific uptake into DCs is achieved after incubation in human blood plasma, proving an efficient combination of "stealth" and targeting after simple adsorption of the PPEs. This strategy can transform any Nanocarrier into DC-targeting by noncovalent adsorption of PPEs and will aid in developing novel immunotherapies.

  • Noncovalent Targeting of Nanocarriers to Immune Cells with Polyphosphoester‐Based Surfactants in Human Blood Plasma
    Advanced science (Weinheim Baden-Wurttemberg Germany), 2019
    Co-Authors: Johanna Simon, Volker Mailander, Katharina Landfester, Kristin N. Bauer, Jens Langhanki, Till Opatz, Frederik R. Wurm
    Abstract:

    Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T-cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the Nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to Nanocarriers requires new chemistry for each Nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the Nanocarriers' surface resulting in specific uptake into DCs combined with low protein adsorption of PPEs is presented. PPEs with hydrophobic anchors and multiple mannose units are reported and adsorbed to different model Nanocarriers. Their protein corona remain similar to pure stealth Nanocarriers and prove only low uptake into nontargeted cells (monocytes). Due to the "stealth" properties of PPEs, a high specific uptake into DCs is achieved after incubation in human blood plasma, proving an efficient combination of "stealth" and targeting after simple adsorption of the PPEs. This strategy can transform any Nanocarrier into DC-targeting by noncovalent adsorption of PPEs and will aid in developing novel immunotherapies.

  • prevention of dominant igg adsorption on Nanocarriers in igg enriched blood plasma by clusterin precoating
    Advanced Science, 2019
    Co-Authors: Domenik Prozeller, Jorge Pereira, Johanna Simon, Volker Mailander, Svenja Morsbach, Katharina Landfester
    Abstract:

    : Nanocarriers for medical applications must work reliably within organisms, independent of the individual differences in the blood proteome. Variation in the blood proteome, such as immunoglobulin levels, is a result of environmental, nutrition, and constitution conditions. This variation, however, should not influence the behavior of Nanocarriers in biological media. The composition of the protein corona is investigated to understand the influence varying immunoglobulin levels in the blood plasma have on the interactions with Nanocarriers. Specifically, the composition of the Nanocarriers' coronas is analyzed after incubation in plasma with normal or elevated immunoglobulin G (IgG) levels, and cellular uptake is monitored in cell lines containing different immunoglobulin receptors. Here, it is reported that upon doubling the IgG concentration in plasma, the IgG fraction in the protein corona increases by a factor of 40 independent of the Nanocarrier material. This results in a significant increase in uptake in cells exhibiting IgG binding receptors. Furthermore, precoating Nanocarriers with clusterin successfully prevents dominant IgG-adsorption and additionally reduces cellular internalization, after incubation with IgG-enriched plasma. Therefore, precoating Nanocarriers may be utilized as a powerful method to reduce the influence of individual variations in blood composition on the protein corona.

Derek Renshaw - One of the best experts on this subject based on the ideXlab platform.

  • Novel potato protein-polysaccharide nano-formulations for oral nutrient delivery
    2016
    Co-Authors: M. Zariwala, Sebastien Farnaud, Satyanarayana Somavarapu, Robert W. Evans, Derek Renshaw
    Abstract:

    Title: Novel potato protein-polysaccharide nano-formulations for oral nutrient delivery Study Objective(s): Bioactive molecules (minerals, vitamins and phytochemicals) have diverse health promoting effects and are used to supplement diet as nutraceuticals. The potential health benefits of several nutraceuticals are limited by lack of stability, reduced activity and low bioavailability. Nano-formulation presents an appealing means of preserving beneficial characteristics while potentially enhancing absorption and potency. Food derived biopolymers such as proteins and polysaccharides are relatively inexpensive, biocompatible, and already used widely in food/ nutraceutical industries. They thus present an attractive resource to formulate nano-vehicles for stabilisation and delivery of nutraceutical bioactives. The aim of our study was to use novel natural source food derived ingredients to formulate Nanocarriers for nutrient delivery applications. Iron was selected as a model nutrient for our initial study since i.) iron has a poor sensory profile ii.) is highly reactive rendering it particularly challenging to formulate iii.) iron deficiency is the most common nutritional deficiency worldwide. Method: Nanocarriers incorporating ferrous sulphate (FeSO4 elemental iron equivalent; Fe) and corresponding iron free (BLANK) were prepared by modified nanoprecipitation method with varying protein : polysaccharide ratios. Batches (4) of Nanocarriers were formulated with potato protein isolate (PP, ≥95% protein content) and two varieties of the crustacean derived natural polysaccharide chitosan (chitosan HCL – CH; chitosan oligosaccharide – CO): i.) PP+CH-Fe ii.) PP+CH-BLANK ii.) PP+CO-Fe iv.) PP+CO-BLANK. Nanocarrier iron incorporation efficiency was determined by colourimetric iron detection. Nanocarrier physiochemical characteristics were assessed by particle size, zeta potential and transmission electron microscopy analysis. Cellular uptake was evaluated using the human intestinal cell line caco-2 in simulated gastrointestinal fluid and cytotoxicity was determined in presence of increasing concentrations of BLANK and iron loaded Nanocarriers (upto 48 hour time-point). Gut pathogenic microbe access to nanoentrapped iron was determined by comparative of growth measurement at 600 nm. Results: Novel potato protein-chitosan blend Nanocarriers were successfully fabricated using our optimised protocol. Nanocarriers demonstrated high iron entrapment efficiency (>80%), rounded morphology and a submicron size range (

  • ascorbyl palmitate dspe peg Nanocarriers for oral iron delivery preparation characterisation and in vitro evaluation
    Colloids and Surfaces B: Biointerfaces, 2014
    Co-Authors: M. Zariwala, Sebastien Farnaud, Zahra Merchant, Satyanarayana Somavarapu, Derek Renshaw
    Abstract:

    The objective of this study was to encapsulate iron in Nanocarriers formulated with ascorbyl palmitate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol (DSPE-PEG) for oral delivery. Blank and iron (Fe) loaded Nanocarriers were prepared by a modified thin film method using ascorbyl palmitate and DSPE-PEG. Surface charge of the Nanocarriers was modified by the inclusion of chitosan (CHI) during the formulation process. Blank and iron loaded ascorbyl palmitate/DSPE Nanocarriers were visualised by transmission electron microscopy (TEM) and physiochemical characterisations of the Nanocarriers carried out to determine the mean particle size and zeta potential. Inclusion of chitosan imparted a net positive charge on the Nanocarrier surface and also led to an increase in mean particle size. Iron entrapment in ascorbyl palmitate-Fe and ascorbyl palmitate-CHI-Fe Nanocarriers was 67% and 76% respectively, suggesting a beneficial effect of chitosan on Nanocarrier Fe entrapment. Iron absorption was estimated by measuring Caco-2 cell ferritin formation using ferrous sulphate as a reference standard. Iron absorption from ascorbyl palmitate-Fe (592.17 ± 21.12 ng/mg cell protein) and ascorbyl palmitate-CHI-Fe (800.12 ± 47.6 ng/mg, cell protein) Nanocarriers was 1.35-fold and 1.5-fold higher than that from free ferrous sulphate, respectively (505.74 ± 23.73 ng/mg cell protein) (n = 6, p < 0.05). This study demonstrates for the first time preparation and characterisation of iron loaded ascorbyl palmitate/DSPE PEG Nanocarriers, and that engineering of the Nanocarriers with chitosan leads to a significant augmentation of iron absorption.

  • Ascorbyl palmitate/DSPE-PEG Nanocarriers for oral iron delivery: Preparation, characterisation and in vitro evaluation
    Colloids and surfaces. B Biointerfaces, 2013
    Co-Authors: M. Zariwala, Sebastien Farnaud, Zahra Merchant, Satyanarayana Somavarapu, Derek Renshaw
    Abstract:

    The objective of this study was to encapsulate iron in Nanocarriers formulated with ascorbyl palmitate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol (DSPE-PEG) for oral delivery. Blank and iron (Fe) loaded Nanocarriers were prepared by a modified thin film method using ascorbyl palmitate and DSPE-PEG. Surface charge of the Nanocarriers was modified by the inclusion of chitosan (CHI) during the formulation process. Blank and iron loaded ascorbyl palmitate/DSPE Nanocarriers were visualised by transmission electron microscopy (TEM) and physiochemical characterisations of the Nanocarriers carried out to determine the mean particle size and zeta potential. Inclusion of chitosan imparted a net positive charge on the Nanocarrier surface and also led to an increase in mean particle size. Iron entrapment in ascorbyl palmitate-Fe and ascorbyl palmitate-CHI-Fe Nanocarriers was 67% and 76% respectively, suggesting a beneficial effect of chitosan on Nanocarrier Fe entrapment. Iron absorption was estimated by measuring Caco-2 cell ferritin formation using ferrous sulphate as a reference standard. Iron absorption from ascorbyl palmitate-Fe (592.17 ± 21.12 ng/mg cell protein) and ascorbyl palmitate-CHI-Fe (800.12 ± 47.6 ng/mg, cell protein) Nanocarriers was 1.35-fold and 1.5-fold higher than that from free ferrous sulphate, respectively (505.74 ± 23.73 ng/mg cell protein) (n = 6, p < 0.05). This study demonstrates for the first time preparation and characterisation of iron loaded ascorbyl palmitate/DSPE PEG Nanocarriers, and that engineering of the Nanocarriers with chitosan leads to a significant augmentation of iron absorption.

Volker Mailander - One of the best experts on this subject based on the ideXlab platform.

  • brush conformation of polyethylene glycol determines the stealth effect of Nanocarriers in the low protein adsorption regime
    Nano Letters, 2021
    Co-Authors: Shuai Jiang, Johanna Simon, Volker Mailander, David Paslick, Marieluise Frey, Manfred Wagner, Daniel Crespy
    Abstract:

    For Nanocarriers with low protein affinity, we show that the interaction of Nanocarriers with cells is mainly affected by the density, the molecular weight, and the conformation of polyethylene glycol (PEG) chains bound to the Nanocarrier surface. We achieve a reduction of nonspecific uptake of ovalbumin Nanocarriers by dendritic cells using densely packed PEG chains with a "brush" conformation instead of the collapsed "mushroom" conformation. We also control to a minor extent the dysopsonin adsorption by tailoring the conformation of attached PEG on the Nanocarriers. The brush conformation of PEG leads to a stealth behavior of the Nanocarriers with inhibited uptake by phagocytic cells, which is a prerequisite for successful in vivo translation of nanomedicine to achieve long blood circulation and targeted delivery. We can clearly correlate the brush conformation of PEG with inhibited phagocytic uptake of the Nanocarriers. This study shows that, in addition to the surface's chemistry, the conformation of polymers controls cellular interactions of the Nanocarriers.

  • noncovalent targeting of Nanocarriers to immune cells with polyphosphoester based surfactants in human blood plasma
    Advanced Science, 2019
    Co-Authors: Johanna Simon, Volker Mailander, Katharina Landfester, Kristin N. Bauer, Jens Langhanki, Till Opatz, Frederik R. Wurm
    Abstract:

    Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T-cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the Nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to Nanocarriers requires new chemistry for each Nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the Nanocarriers' surface resulting in specific uptake into DCs combined with low protein adsorption of PPEs is presented. PPEs with hydrophobic anchors and multiple mannose units are reported and adsorbed to different model Nanocarriers. Their protein corona remain similar to pure stealth Nanocarriers and prove only low uptake into nontargeted cells (monocytes). Due to the "stealth" properties of PPEs, a high specific uptake into DCs is achieved after incubation in human blood plasma, proving an efficient combination of "stealth" and targeting after simple adsorption of the PPEs. This strategy can transform any Nanocarrier into DC-targeting by noncovalent adsorption of PPEs and will aid in developing novel immunotherapies.

  • Noncovalent Targeting of Nanocarriers to Immune Cells with Polyphosphoester‐Based Surfactants in Human Blood Plasma
    Advanced science (Weinheim Baden-Wurttemberg Germany), 2019
    Co-Authors: Johanna Simon, Volker Mailander, Katharina Landfester, Kristin N. Bauer, Jens Langhanki, Till Opatz, Frederik R. Wurm
    Abstract:

    Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T-cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the Nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to Nanocarriers requires new chemistry for each Nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the Nanocarriers' surface resulting in specific uptake into DCs combined with low protein adsorption of PPEs is presented. PPEs with hydrophobic anchors and multiple mannose units are reported and adsorbed to different model Nanocarriers. Their protein corona remain similar to pure stealth Nanocarriers and prove only low uptake into nontargeted cells (monocytes). Due to the "stealth" properties of PPEs, a high specific uptake into DCs is achieved after incubation in human blood plasma, proving an efficient combination of "stealth" and targeting after simple adsorption of the PPEs. This strategy can transform any Nanocarrier into DC-targeting by noncovalent adsorption of PPEs and will aid in developing novel immunotherapies.

  • prevention of dominant igg adsorption on Nanocarriers in igg enriched blood plasma by clusterin precoating
    Advanced Science, 2019
    Co-Authors: Domenik Prozeller, Jorge Pereira, Johanna Simon, Volker Mailander, Svenja Morsbach, Katharina Landfester
    Abstract:

    : Nanocarriers for medical applications must work reliably within organisms, independent of the individual differences in the blood proteome. Variation in the blood proteome, such as immunoglobulin levels, is a result of environmental, nutrition, and constitution conditions. This variation, however, should not influence the behavior of Nanocarriers in biological media. The composition of the protein corona is investigated to understand the influence varying immunoglobulin levels in the blood plasma have on the interactions with Nanocarriers. Specifically, the composition of the Nanocarriers' coronas is analyzed after incubation in plasma with normal or elevated immunoglobulin G (IgG) levels, and cellular uptake is monitored in cell lines containing different immunoglobulin receptors. Here, it is reported that upon doubling the IgG concentration in plasma, the IgG fraction in the protein corona increases by a factor of 40 independent of the Nanocarrier material. This results in a significant increase in uptake in cells exhibiting IgG binding receptors. Furthermore, precoating Nanocarriers with clusterin successfully prevents dominant IgG-adsorption and additionally reduces cellular internalization, after incubation with IgG-enriched plasma. Therefore, precoating Nanocarriers may be utilized as a powerful method to reduce the influence of individual variations in blood composition on the protein corona.

  • Phosphonylation Controls the Protein Corona of Multifunctional Polyglycerol-Modified Nanocarriers.
    Macromolecular bioscience, 2019
    Co-Authors: Ann Kathrin Danner, Volker Mailander, Svenja Morsbach, Katharina Landfester, Susanne Schöttler, Evandro M. Alexandrino, Sophie Hammer, Holger Frey, Frederik R. Wurm
    Abstract:

    Nanocarriers are a platform for modern drug delivery. In contact with blood, proteins adsorb to Nanocarriers, altering their behavior in vivo. To reduce unspecific protein adsorption and unspecific cellular uptake, Nanocarriers are modified with hydrophilic polymers like poly(ethylene glycol) (PEG). However, with PEG the attachment of further functional structures such as targeting units is limited. A method to introduce multifunctionality via polyglycerol (PG) while maintaining the hydrophilicity of PEG is introduced. Different amounts of negatively charged phosphonate groups (up to 29 mol%) are attached to the multifunctional PGs (Mn 2-4 kg mol-1 , Ð < 1.36) by post-modification. PGs are used in the miniemulsion/solvent evaporation procedure to prepare model Nanocarriers. Their behavior in human blood plasma is investigated to determine the influence of the negative charges on the protein adsorption. The protein corona of PGylated Nanocarriers is similar to PEGylated analogs (on same Nanocarriers), but the protein pattern could be gradually altered by the integration of phosphonates. This is the first report on the gradual increase of negative charges on Nanocarriers and intriguingly up to a certain amount of phosphonate groups per Nanocarrier the protein pattern remains relatively unchanged, which is important for the future design of Nanocarriers.

Junjie Zhu - One of the best experts on this subject based on the ideXlab platform.

  • dna hybrid gated multifunctional mesoporous silica Nanocarriers for dual targeted and microrna responsive controlled drug delivery
    Angewandte Chemie, 2014
    Co-Authors: Penghui Zhang, Fangfang Cheng, Ri Zhou, Juntao Cao, Jingjing Li, Clemens Burda, Qianhao Min, Junjie Zhu
    Abstract:

    The design of an ideal drug delivery system with targeted recognition and zero premature release, especially controlled and specific release that is triggered by an exclusive endogenous stimulus, is a great challenge. A traceable and aptamer-targeted drug Nanocarrier has now been developed; the Nanocarrier was obtained by capping mesoporous silica-coated quantum dots with a programmable DNA hybrid, and the drug release was controlled by microRNA. Once the Nanocarriers had been delivered into HeLa cells by aptamer-mediated recognition and endocytosis, the overexpressed endogenous miR-21 served as an exclusive key to unlock the Nanocarriers by competitive hybridization with the DNA hybrid, which led to a sustained lethality of the HeLa cells. If microRNA that is exclusively expressed in specific pathological cell was screened, a combination of chemotherapy and gene therapy should pave the way for a targeted and personalized treatment of human diseases.

  • DNA‐Hybrid‐Gated Multifunctional Mesoporous Silica Nanocarriers for Dual‐Targeted and MicroRNA‐Responsive Controlled Drug Delivery
    Angewandte Chemie International Edition, 2014
    Co-Authors: Penghui Zhang, Fangfang Cheng, Ri Zhou, Juntao Cao, Clemens Burda, Qianhao Min, Junjie Zhu
    Abstract:

    The design of an ideal drug delivery system with targeted recognition and zero premature release, especially controlled and specific release that is triggered by an exclusive endogenous stimulus, is a great challenge. A traceable and aptamer-targeted drug Nanocarrier has now been developed; the Nanocarrier was obtained by capping mesoporous silica-coated quantum dots with a programmable DNA hybrid, and the drug release was controlled by microRNA. Once the Nanocarriers had been delivered into HeLa cells by aptamer-mediated recognition and endocytosis, the overexpressed endogenous miR-21 served as an exclusive key to unlock the Nanocarriers by competitive hybridization with the DNA hybrid, which led to a sustained lethality of the HeLa cells. If microRNA that is exclusively expressed in specific pathological cell was screened, a combination of chemotherapy and gene therapy should pave the way for a targeted and personalized treatment of human diseases.