Multi-stimuli-responsive aggregation of nanoparticles driven by the manipulation of colloidal stability

Johnson, Luke R.; Gray, Dominic M.; Niezabitowska, Edyta; McDonald, Tom O.

doi:10.1039/d1nr01190a

Cited by 36 publications

(37 citation statements)

References 132 publications

(157 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adding flocculants, allowed EVs to precipitate in a controlled manner leading to enhanced interaction with antibody-coated surfaces. Since charged polymers were used, it could be anticipated that the interaction would be reversible and aggregates could be dissociated by successive washes, performed after the immunocapture step as it has been demonstrated previously [ 46 – 48 ]. This would be a clear advantage compared to other polymers commonly used for EV precipitation, such as polyethylene glycol (PEG), a non-ionic uncharged hydrophilic polymer, whose water excluding properties create a high osmotic pressure causing irreversible protein precipitation in complex solutions [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

A simple immunoassay for extracellular vesicle liquid biopsy in microliters of non-processed plasma

et al. 2022

View full text Add to dashboard Cite

Background Extracellular vesicles (EVs), released by most cell types, provide an excellent source of biomarkers in biological fluids. However, in order to perform validation studies and screenings of patient samples, it is still necessary to develop general techniques permitting rapid handling of small amounts of biological samples from large numbers of donors. Results Here we describe a method that, using just a few microliters of patient’s plasma, identifies tumour markers exposed on EVs. Studying physico-chemical properties of EVs in solution, we demonstrate that they behave as stable colloidal suspensions and therefore, in immunocapture assays, many of them are unable to interact with a stationary functionalised surface. Using flocculation methods, like those used to destabilize colloids, we demonstrate that cationic polymers increase EV ζ-potential, diameter, and sedimentation coefficient and thus, allow a more efficient capture on antibody-coated surfaces by both ELISA and bead-assisted flow cytometry. These findings led to optimization of a protocol in microtiter plates allowing effective immunocapture of EVs, directly in plasma without previous ultracentrifugation or other EV enrichment. The method, easily adaptable to any laboratory, has been validated using plasma from lung cancer patients in which the epithelial cell marker EpCAM has been detected on EVs. Conclusions This optimized high throughput, easy to automate, technology allows screening of large numbers of patients to phenotype tumour markers in circulating EVs, breaking barriers for the validation of proposed EV biomarkers and the discovery of new ones. Graphical Abstract

show abstract

Section: Discussionmentioning

confidence: 99%

A simple immunoassay for extracellular vesicle liquid biopsy in microliters of non-processed plasma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…[80] The NP created herein has properties balanced between efficient cytosolic release of nucleic acid and colloid stability in vivo. The core-shell GNPs attained colloid stability through dense coating by GCS polymer brushes that provided steric stabilization when swelling in water [81]. Our results indicate that GNPs containing higher amounts of GC exhibit greater colloidal stability under physiologic conditions.…”

Section: Discussionmentioning

confidence: 75%

A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects

et al. 2022

View full text Add to dashboard Cite

The inherent instability of nucleic acids within serum and the tumor microenvironment necessitates a suitable vehicle for non-viral gene delivery to malignant lesions. A specificity-conferring mechanism is also often needed to mitigate off-target toxicity. In the present study, we report a stable and efficient redox-sensitive nanoparticle system with a unique core–shell structure as a DNA carrier for cancer theranostics. Thiolated polyethylenimine (PEI-SH) is complexed with DNA through electrostatic interactions to form the core, and glycol chitosan-modified with succinimidyl 3-(2-pyridyldithio)propionate (GCS-PDP) is grafted on the surface through a thiolate-disulfide interchange reaction to form the shell. The resulting nanoparticles, GCS-PDP/PEI-SH/DNA nanoparticles (GNPs), exhibit high colloid stability in a simulated physiological environment and redox-responsive DNA release. GNPs not only show a high and redox-responsive cellular uptake, high transfection efficiency, and low cytotoxicity in vitro, but also exhibit selective tumor targeting, with minimal toxicity, in vivo, upon systemic administration. Such a performance positions GNPs as viable candidates for molecular-genetic imaging and theranostic applications.

show abstract

“…In such cases, nanoparticle formulation can be tailored through incorporation of polymers which disassemble at endosomal pH, promoting endosomal escape, or via the incorporation of cell penetrating molecules, such as peptides which exclusively promote endosomal escape [ 102 ]. Activated upon a fall in pH (4.5–6.0), these nanoparticles enable the release of their cargo within these more acidic environments and subsequent release into the cytoplasm [ 103 , 104 ]. Furthermore, thermosensitive liposomes (e.g.…”

Section: Functionalisation Of Nanomedicinesmentioning

confidence: 99%

Development of next generation nanomedicine-based approaches for the treatment of cancer: we've barely scratched the surface

Tracey

Smyth

Barelle³

et al. 2021

Biochemical Society Transactions

View full text Add to dashboard Cite

Interest in nanomedicines has grown rapidly over the past two decades, owing to the promising therapeutic applications they may provide, particularly for the treatment of cancer. Personalised medicine and ‘smart’ actively targeted nanoparticles represent an opportunity to deliver therapies directly to cancer cells and provide sustained drug release, in turn providing overall lower off-target toxicity and increased therapeutic efficacy. However, the successful translation of nanomedicines from encouraging pre-clinical findings to the clinic has, to date, proven arduous. In this review, we will discuss the use of nanomedicines for the treatment of cancer, with a specific focus on the use of polymeric and lipid nanoparticle delivery systems. In particular, we examine approaches exploring the surface functionalisation of nanomedicines to elicit active targeting and therapeutic effects as well as challenges and future directions for nanoparticles in cancer treatment.

show abstract

Multi-stimuli-responsive aggregation of nanoparticles driven by the manipulation of colloidal stability

Abstract: The capacity to control the dispersed or aggregated state of colloidal particles is particularly attractive for facilitating a diverse range of smart applications. For this reason, stimuli-responsive nanoparticles have garnered...

Cited by 36 publications

References 132 publications

A simple immunoassay for extracellular vesicle liquid biopsy in microliters of non-processed plasma

A simple immunoassay for extracellular vesicle liquid biopsy in microliters of non-processed plasma

A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects

Development of next generation nanomedicine-based approaches for the treatment of cancer: we've barely scratched the surface

Contact Info

Product

Resources

About