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Record W4400782574 · doi:10.1021/acsami.4c08240

Cell Membrane-Derived Nanoparticles as Biomimetic Nanotherapeutics to Alleviate Fatty Liver Disease

2024· article· en· W4400782574 on OpenAlexafffund
Alap Ali Zahid, Aishik Chakraborty, Yasmeen Shamiya, Rachel B. Wilson, Nica M. Borradaile, Arghya Paul

Bibliographic record

VenueACS Applied Materials & Interfaces · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicPhagocytosis and Immune Regulation
Canadian institutionsWestern University
FundersInstitute of Musculoskeletal Health and ArthritisNatural Sciences and Engineering Research Council of CanadaCanada Research ChairsGovernment of CanadaGovernment of Ontario
KeywordsBioavailabilityDrug deliveryHepatocyteDrugMaterials scienceCellRosuvastatinPharmacologyNanotechnologyBiologyBiochemistryIn vitro

Abstract

fetched live from OpenAlex

The prevalence of metabolic dysfunction associated-steatotic liver disease (MASLD) (formerly known as nonalcoholic fatty liver disease; NAFLD) is estimated at around 32% of the world's population, resulting in a major healthcare concern in recent times. Current pharmaceutical methods lack efficacy for the treatment of the disease because of suboptimal pharmacokinetic parameters including poor bioavailability, short half-life, and premature clearance. Designing an efficient drug delivery system that provides a protective environment is critical for addressing these challenges. Such a system should aim to enhance the cellular uptake of drugs, improve their bioavailability, and reduce the chances of rapid clearance. Here, we developed nanoengineered natural cell membrane-derived nanoparticles (CMNs) incorporated with a model drug, rosuvastatin, in the bilayer assembly of CMNs to reduce the accumulation of lipids in hepatocytes, a hallmark of MASLD. We used a cell extrusion technique to develop self-assembled CMNs with precise size control compared to the cell shearing method. Interestingly, the prepared CMNs were found to be nonphagocytic, representing around 1.13% of phosphatidylserine receptors on healthy cells, which allows the possibility of their use as stealth nanoparticles for drug delivery. Furthermore, CMNs exhibit higher drug-loading efficiency, excellent cytocompatibility, and enhanced cellular internalization capabilities. Moreover, we show that the delivery of rosuvastatin-loaded CMNs in the in vitro MASLD model efficiently reduced hepatocyte lipid accumulation, including total cholesterol (26.8 ± 3.1%) and triglycerides (11.8 ± 0.8%), compared to the negative control. Taken together, the nanoengineered biomimetic CMNs enhance the drug's bioactivity in hepatic cells, establishing a foundation for further investigation of this drug delivery system in treating MASLD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.007

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.244
Teacher spread0.229 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; both teacher heads agree on what is shown here.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations14
Published2024
Admission routes2
Has abstractyes

Explore more

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