Intracellular delivery of proteins, peptides and biologics is an emerging field which has the potential to provide novel opportunities to target intracellular proteins, previously deemed 'undruggable'. However, the delivery of proteins intracellularly remains a challenge. Here, we present a cationic nanoparticle delivery system for enhanced cellular delivery of proteins through use of a polyethyleneimine and poly-(lactic--glycolic acid) polymer blend. Cationic nanoparticles were shown to provide increased cellular uptake compared to anionic and neutral nanoparticles, successfully delivering Variable New Antigen Receptors (vNARs), entrapped within the nanoparticle core, to the cell interior. vNARs were identified as ideal candidates for nanoparticle entrapment due to their remarkable stability. The optimised 10% PEI-PLGA nanoparticle formulation displayed low toxicity, was uniform in size and possessed appropriate cationic charge to limit cellular toxicity, whilst being capable of escaping the endo/lysosomal system and delivering their cargo to the cytosol. This work demonstrates the ability of cationic nanoparticles to facilitate intracellular delivery of vNARs, novel biologic agents with potential utility towards intracellular targets.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654694 | PMC |
| http://dx.doi.org/10.1039/d3ra06050k | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Degradable Theranostic Polyurethane for Macrophage-Targeted Antileishmanial Drug Delivery.
Biomacromolecules
January 2025
Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Nadia, Mohanpur 741246, West Bengal, India.
The present investigation aims to develop a reactive oxygen species (ROS) and esterase-responsive biodegradable mannosylated polyurethane to effectively deliver the encapsulated antileishmanial drug amphotericin B (AmB) selectively to infected macrophage cells. Owing to suitable amphiphilic balance, the as-synthesized glycosylated polyurethane () with aryl boronic ester-based diol () moiety as ROS-trigger, water-soluble mannose pendants, and fluorescent 4,4-difluoro-4-bora-3a,4a-diaza--indacene (BODIPY) chain ends for bioimaging formed nanoaggregates in an aqueous medium as confirmed by H NMR spectroscopy, dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and critical aggregation concentration (CAC) measurements. Aided by two endogenous stimuli present in phagolysosome, ROS and esterase, AmB-encapsulated polymeric nanoaggregates as drug delivery vehicles achieved an efficient reduction of both and intracellular amastigote burden compared to the free AmB.
View Article and Find Full Text PDFTerahertz Wave Desensitizes Ferroptosis by Inhibiting the Binding of Ferric Ions to the Transferrin.
ACS Nano
January 2025
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
Ferroptosis is a classic type of programmed cell death characterized by iron dependence, which is closely associated with many diseases such as cancer, intestinal ischemic diseases, and nervous system diseases. Transferrin (Tf) is responsible for ferric-ion delivery owing to its natural Fe binding ability and plays a crucial role in ferroptosis. However, Tf is not considered as a classic druggable target for ferroptosis-associated diseases since systemic perturbation of Tf would dramatically disrupt blood iron homeostasis.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Alabama at Birmingham, Birmingham, AL, USA.
Progranulin is a secreted pro-protein that is necessary for maintaining lysosomal function and exerts anti-inflammatory and neurotrophic effects in the brain. Loss-of-function GRN mutations, most of which cause progranulin haploinsufficiency, are a major autosomal dominant cause of frontotemporal dementia (FTD). Other GRN variants are associated with risk for FTD, Alzheimer's disease (AD) and Parkinson's disease.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Background: Despite recent FDA approvement of disease-modifying treatments that reduce Aβ, the identification of novel therapeutic strategies that could delay the Alzheimer's disease (AD) development are needed. We identified and developed novel small molecule compounds that mildly inhibit mitochondrial complex I (MCI). Chronic treatment with a tool compound CP2 in 4 mouse models of familial AD was efficacious protecting against synaptic dysfunction and memory impairment, improving brain energetics and cognitive performance, reducing levels of human pTau and Ab.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
Background: Monoclonal antibodies have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer's disease. Such antibodies, however, are expensive and timely to produce and require frequent dosing regimens to ensure disease-modifying effects. Synthetic in vitro-transcribed mRNA encoding antibodies presents a promising alternative to conventional passive immunotherapy and overcomes the need to generate recombinant antibodies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!