Intracellular plasmid DNA delivery by self-assembled nanoparticles of amphiphilic PHML- <i>b</i> -PLLA- <i>b</i> -PHML copolymers and the endocytosis pathway analysis
Bibliographic record
Abstract
This work presents a new series of polycationic nanoparticles of ( l-)-lysine conjugated amphiphilic triblock copolymer poly(hydroxyletheyl methacrylate-L-lysine)- b-poly(L-lactide)- b-poly(hydroxyletheyl methacrylate-L-lysine)s (PHML- b-PLLA- b-PHML) as potent low cytotoxic vectors for intracellular plasmid DNA delivery. First, the triblock PHML- b-PLLA- b-PHML copolymers were prepared via a combination of metal-free controlled ring opening polymerization and successive atom transfer radical polymerization. Then the cationic PHML- b-PLLA- b-PHML nanoparticles were further prepared by solution self-assembly. The particle size, zeta potential and morphology of as-prepared PHML- b-PLLA- b-PHML nanoparticles were characterized by dynamic light scattering and atomic force microscopy, respectively. The plasmid DNA binding affinities and polyplex stabilities were separately explored by agarose gel retardation and DNase I degradation assays. Then in vitro cytotoxicity and gene transfection efficiency of the PHML- b-PLLA- b-PHML nanoparticles vectors as well as relevant polyplex endocytosis pathway were investigated with H1299 cells. It was revealed that the PHML- b-PLLA- b-PHML nanoparticles exhibited low cytotoxicity, strong plasmid DNA binding affinity, high polyplex stability and efficient plasmid DNA transfection even under serum conditions (10% FBS). Moreover, the endocytosis analysis results disclosed that the PHML 30 - b-PLLA- b-PHML 30 nanoparticle/plasmid DNA polyplexes were predominantly involved in lipid-raft-mediated endocytosis pathway, similar to that of SV40 virus-based vectors.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 source (direct Gemma or distilled Codex), 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".