Membrane lipids destabilize short interfering ribonucleic acid (siRNA)/polyethylenimine nanoparticles
Bibliographic record
Abstract
Cell entry of polymeric nanoparticles (NPs) bearing polynucleotides is an important stage for successful gene delivery. In this work, we addressed the influence of cell membrane lipids on the integrity and configurational changes of NPs composed of short interfering ribonucleic acid (siRNA) and polyethylenimine. We focused on NPs derived from two different PEIs, unmodified low molecular weight PEI and linoleic acid (LA)-substituted PEI, and their interactions with two membrane lipids (zwitterionic 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) and anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS)). Our experiments showed that POPS liposomes interacted strongly with both types of NPs, which caused partial dissociation of the NPs. POPC liposomes, however, did not induce any dissociation. Consistent with the experiments, steered molecular dynamics simulations showed a stronger interaction between the NPs and the POPS membrane than between the NPs and the POPC membrane. Lipid substitution on the PEIs enhanced the stability of the NPs during membrane crossing; lipid association between PEIs of the LA-bearing NPs as well as parallel orientation of the siRNAs provided protection against their dissociation (unlike NPs from native PEI). Our observations provide valuable insight into the integrity and structural changes of PEI/siRNA NPs during membrane crossing which will help in the design of more effective carriers for nucleic acid delivery.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".