Theranostic porphyrin nanoparticles identify atherosclerosis via multimodal imaging and elicit atheroprotective effects
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Background Porphyrin-lipid nanoparticles (Por-NPs) have unrealized potential for atherosclerosis. Por-NPs incorporate porphyrin-lipid which permits fluorescence imaging and chelates Copper-64 ( 64 Cu) for positron emission tomography (PET) imaging. Their outer shell contains a short peptide ‘R4F’ that enables macrophage targeting and therapeutic effects. Accordingly, this study investigates the simultaneous diagnostic and therapeutic properties of Por-NPs in atherosclerosis. Results In vitro , Por-NPs were found to be internalised by immortalised bone marrow-derived macrophages (iBMDMs), visualised via fluorescence microscopy and flow cytometry. Por-NPs also increased cholesterol efflux from [ 3 H]-cholesterol-loaded iBMDMs, (49%, P <0.05). Incubation of iBMDMs with Por-NPs reduced mRNA levels of inflammatory mediators Il1b (88%), Il18 (54%) Ccl5 (75%) and Ccl17 (92%), and protein secretion of IL-1β (69%), CCL5 (82%) and CCL17 (94%), P <0.05. Por-NPs suppressed inflammasome components Nlrp3 (69%) and Asc (36%), P <0.05. Studies using siRNA deletion of SR-B1 and methyl-β-cyclodextrin, revealed the anti-inflammatory properties of Por-NPs were independent of SR-B1 and cholesterol efflux. However, Por-NPs suppressed activation of inflammatory transcription factor NF-κB (53%, P <0.05). In vivo , in Apoe -/- mice, serial non-invasive PET imaging showed 64 Cu-labelled Por-NPs localised in hearts and detected increases in plaque size longitudinally with high-cholesterol diet. Por-NP fluorescence was visualised in aortic sinus plaques, co-localised with CD68 + macrophages, and by fluorescence IVIS imaging in aortic arch plaque. In two murine models, Por-NP-treated mice had smaller early-stage (22%) and unstable plaques (52%). Por-NP-treated mice had fewer circulating (32%) and aortic (81%) monocytes, and lower mRNA levels of aortic arch Rela (26%) and Nfkb1 (27%), P <0.05. Conclusions Por-NPs detect plaques using multiple imaging modalities and exhibit atheroprotective effects, presenting as novel nanoscale theranostics for atherosclerosis.
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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 it