scholarly journals Simultaneous Exposure of Different Nanoparticles Influences Cell Uptake

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 136
Author(s):  
Isa de Boer ◽  
Ceri J. Richards ◽  
Christoffer Åberg
Keyword(s):  
Drug Delivery ◽  
Individual Cell ◽  
Model System ◽  
Cell Uptake ◽  
Target Cells ◽  
Cell Level ◽  
Polystyrene Nanoparticles ◽  
Simultaneous Exposure ◽  
Different Types ◽  
Uptake Studies

Drug delivery using nano-sized carriers holds tremendous potential for curing a range of diseases. The internalisation of nanoparticles by cells, however, remains poorly understood, restricting the possibility for optimising entrance into target cells, avoiding off-target cells and evading clearance. The majority of nanoparticle cell uptake studies have been performed in the presence of only the particle of interest; here, we instead report measurements of uptake when the cells are exposed to two different types of nanoparticles at the same time. We used carboxylated polystyrene nanoparticles of two different sizes as a model system and exposed them to HeLa cells in the presence of a biomolecular corona. Using flow cytometry, we quantify the uptake at both average and individual cell level. Consistent with previous literature, we show that uptake of the larger particles is impeded in the presence of competing smaller particles and, conversely, that uptake of the smaller particles is promoted by competing larger particles. While the mechanism(s) underlying these observations remain(s) undetermined, we are partly able to restrain the likely possibilities. In the future, these effects could conceivably be used to enhance uptake of nano-sized particles used for drug delivery, by administering two different types of particles at the same time.

scholarly journals Stimulus-responsive liposomes as smart nanoplatforms for drug delivery applications

2018 ◽  
Vol 7 (1) ◽  
pp. 95-122 ◽  
Author(s):  
Parham Sahandi Zangabad ◽  
Soroush Mirkiani ◽  
Shayan Shahsavari ◽  
Behrad Masoudi ◽  
Maryam Masroor ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Target Cells ◽  
Stimulus Responsive ◽  
Different Types ◽  
Drug Delivery Applications ◽  
The Individual ◽  
Chemical Groups ◽  
External Stimuli ◽  
Toxic Drugs ◽  
Modification Of The Surface

AbstractLiposomes are known to be promising nanoparticles (NPs) for drug delivery applications. Among the different types of self-assembled NPs, liposomes stand out for their non-toxic nature and their possession of dual hydrophilic-hydrophobic domains. The advantages of liposomes include the ability to solubilize hydrophobic drugs, the ability to incorporate different hydrophilic and lipophilic drugs at the same time, lessening the exposure of host organs to potentially toxic drugs and allowing modification of the surface by a variety of different chemical groups. This modification of the surface, or of the individual constituents, may be used to achieve two important goals. First, ligands for active targeting can be attached that are recognized by cognate receptors overexpressed on the target cells of tissues. Second, modification can be used to impart a stimulus-responsive or “smart” character to the liposomes, whereby the cargo is released on demand only when certain internal stimuli (pH, reducing agents, specific enzymes) or external stimuli [light, magnetic field, or ultrasound (US)] are present. Here, we review the field of smart liposomes for drug delivery applications.

scholarly journals Combined Method to Remove Endotoxins from Protein Nanocages for Drug Delivery Applications: The Case of Human Ferritin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 229
Author(s):  
Filippo Silva ◽  
Leopoldo Sitia ◽  
Raffaele Allevi ◽  
Arianna Bonizzi ◽  
Marta Sevieri ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Biological Fluids ◽  
Affinity Purification ◽  
Delivery Systems ◽  
Point Of View ◽  
Uniform Structure ◽  
Structure Stability ◽  
Target Cells ◽  
Clinical Phase ◽  
Main Challenge

Protein nanocages represent an emerging candidate among nanoscaled delivery systems. Indeed, they display unique features that proved to be very interesting from the nanotechnological point of view such as uniform structure, stability in biological fluids, suitability for surface modification to insert targeting moieties and loading with different drugs and dyes. However, one of the main concerns regards the production as recombinant proteins in E. coli, which leads to a product with high endotoxin contamination, resulting in nanocage immunogenicity and pyrogenicity. Indeed, a main challenge in the development of protein-based nanoparticles is finding effective procedures to remove endotoxins without affecting protein stability, since every intravenous injectable formulation that should be assessed in preclinical and clinical phase studies should display endotoxins concentration below the admitted limit of 5 EU/kg. Different strategies could be employed to achieve such a result, either by using affinity chromatography or detergents. However, these strategies are not applicable to protein nanocages as such and require implementations. Here we propose a combined protocol to remove bacterial endotoxins from nanocages of human H-ferritin, which is one of the most studied and most promising protein-based drug delivery systems. This protocol couples the affinity purification with the Endotrap HD resin to a treatment with Triton X-114. Exploiting this protocol, we were able to obtain excellent levels of purity maintaining good protein recovery rates, without affecting nanocage interactions with target cells. Indeed, binding assay and confocal microscopy experiments confirm that purified H-ferritin retains its capability to specifically recognize cancer cells. This procedure allowed to obtain injectable formulations, which is preliminary to move to a clinical trial.

scholarly journals FlsnRNA-seq: protoplasting-free full-length single-nucleus RNA profiling in plants

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanping Long ◽  
Zhijian Liu ◽  
Jinbu Jia ◽  
Weipeng Mo ◽  
Liang Fang ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Walls ◽  
Large Scale ◽  
Full Length ◽  
Cell Level ◽  
Root Cells ◽  
Rna Profiling ◽  
Different Types ◽  
Long Read ◽  
Single Nucleus

AbstractThe broad application of single-cell RNA profiling in plants has been hindered by the prerequisite of protoplasting that requires digesting the cell walls from different types of plant tissues. Here, we present a protoplasting-free approach, flsnRNA-seq, for large-scale full-length RNA profiling at a single-nucleus level in plants using isolated nuclei. Combined with 10x Genomics and Nanopore long-read sequencing, we validate the robustness of this approach in Arabidopsis root cells and the developing endosperm. Sequencing results demonstrate that it allows for uncovering alternative splicing and polyadenylation-related RNA isoform information at the single-cell level, which facilitates characterizing cell identities.

scholarly journals Synthesis and tumour cell uptake studies of gadolinium(III)–phosphonium complexes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew J. Hall ◽  
Amy G. Robertson ◽  
Leila R. Hill ◽  
Louis M. Rendina
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumour Cell ◽  
In Vitro Cytotoxicity ◽  
Cell Uptake ◽  
Solution Stability ◽  
T98g Cell ◽  
Human Glioblastoma Multiforme ◽  
Theranostic Agents ◽  
Uptake Studies

AbstractThe synthesis of a new series of Gd(III)-arylphosphonium complexes is described and the solution stability of selected compounds is reported. Their lipophilicity and uptake in human glial (SVG p12) and human glioblastoma multiforme (T98G) cell lines are presented. The in vitro cytotoxicity of all complexes was determined to be low at therapeutically-relevant concentrations. Selected Gd(III) complexes are potential candidates for further investigation as theranostic agents.

scholarly journals Mesoporous Silica Nanoparticles: Their Projection in Nanomedicine

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
María Vallet-Regí
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Surrounding Medium ◽  
Stimuli Responsive ◽  
Guest Molecules ◽  
Different Types ◽  
Potential Applications ◽  
Inorganic Nanomaterials

Mesoporous silica nanoparticles are receiving growing attention by the scientific biomedical community. Among the different types of inorganic nanomaterials, mesoporous silica nanoparticles have emerged as promising multifunctional platforms for nanomedicine. Since their introduction in the drug delivery landscape in 2001, mesoporous materials for drug delivery are receiving growing scientific interest for their potential applications in the biotechnology and nanomedicine fields. The ceramic matrix efficiently protects entrapped guest molecules against enzymatic degradation or denaturation induced by pH and temperature as no swelling or porosity changes take place as a response to variations in the surrounding medium. It is possible to load huge amounts of cargo into the mesopore voids and capping the pore entrances with different nanogates. The application of a stimulus provokes the nanocap removal and triggers the departure of the cargo. This strategy permits the design of stimuli-responsive drug delivery nanodevices.

scholarly journals Extracellular cytolysis by activated macrophages and granulocytes. I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide.

1979 ◽  
Vol 149 (1) ◽  
pp. 84-99 ◽  
Author(s):  
C F Nathan ◽  
L H Brukner ◽  
S C Silverstein ◽  
Z A Cohn
Keyword(s):  
Trypan Blue ◽  
Response Curve ◽  
Target Cells ◽  
Activated Macrophages ◽  
Lymphoma Cells ◽  
Effector Cells ◽  
Proteose Peptone ◽  
Standard Assay ◽  
Different Types ◽  
J774 Cells

Lymphoma cells were rapidly lysed by activated macrophages and granulocytes in the presence of PMA. Release of 51Cr from lymphoma cells correlated closely with their destruction as viewed by scanning electron microscopy, and with reduction in the number of trypan blue-excluding cells. The standard assay involved 51 Cr release measured at 4.5 h, but injury appeared to be complete in 1 h. Of eight different types of effector cells tested, only those releasing abundant H2O2 in response to PMA were effective, that, is BCG-, C. parvum-, or casein-activated macrophages, or thioglycollate-elicited granulocytes. Normal macrophages, J774 cells, or macrophages elicited with thioglycollate broth or proteose-peptone were ineffective. BCG-activated macrophages and granulocytes caused 50% specific release of 51Cr from P388 lymphoma cells at E:T ratios between 1.4 and 4.5, and from mouse erythrocytes at E:T ratios of 0.017 to 0.025. 10 types of target cells varied widely in their susceptibility to lysis by reagent H2O2, with one-half maximal lysis occurring at H2O2 concentrations ranging from 3.63 X 10(-6) M to 3.85 X 10(-5) M. Effector cells were expected to generate approximately that much H2O2 during the period of injury. Susceptibility of the target cells to lysis by PMA-triggered granulocytes correlated closely with their sensitivity to H2O2 (r = 0.98). The membrane-active agents LPS and digitonin, which did not trigger H2O2 release, did not trigger cytotoxicity. The dose-response curve for triggering of H2O2 release by PMA was identical to that for triggering cytotoxicity. These results provided strong circumstantial evidence for the importance of H2O2 in extracellular cytolysis by activated macrophages and granulocytes when pharmacologically triggered.

Recent advances in polymer shell-oily core nanocapsules for drug delivery applications

Nanomedicine ◽  
2021 ◽  
Author(s):  
Ahmed S AbdElhamid ◽  
Dina G Zayed ◽  
Lamia Heikal ◽  
Sherine N Khattab ◽  
Omar Y Mady ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Early Stage ◽  
Controlled Drug Release ◽  
Delivery Systems ◽  
Polymeric Membranes ◽  
Polymer Shell ◽  
Recent Advances ◽  
Target Sites ◽  
Different Types

Polymeric nanocapsules are vesicular drug delivery systems composed of an inner oily reservoir surrounded by polymeric membranes. Nanocapsules have various advantages over other nanovesicular systems such as providing controlled drug release properties. We discuss the recent advances in polymeric shell-oily core nanocapsules, illustrating the different types of polymers used and their implementation. Nanocapsules can be utilized for many purposes, especially encapsulation of highly lipophilic drugs. They have been shown to have variable applications, especially in cancer therapy, due to the ability of the polymeric shell to direct the loaded drugs to their target sites, as well as their high internalization efficacy. Those productive applications guaranteed their high potential as drug delivery systems. However, their clinical development is still in an early stage.

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