Nanoparticles for the Delivery of Pro-regenerative Cardiac Progenitor Secretory Proteins Targeting Cellular Senescence and Vasculogenesis
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Bibliographic record
Abstract
Contemporary therapies following heart failure center on regenerative approaches to account for the loss of cardiomyocytes and limited regenerative capacity of the adult heart. While the delivery of cardiac progenitor cells has been shown to improve cardiac function and repair following injury, recent evidence has suggested that their paracrine effects (or secretome) provides a significant contribution towards modulating regeneration, rather than the progenitor cells intrinsically. The direct delivery of secretory biomolecules, however, remains a challenge due to their lack of stability and tissue retention, limiting their prolonged therapeutic efficacy. We hypothesized that polyurethane-based nanoparticles with heteropolar-hydrophobic-ionic chemistry (DPHI-NPs) could enable the delivery of a subset of pro-regenerative cardiac progenitor cell proteins [bone morphogenetic protein-4 (BMP-4) and angiotensin 1-7 (Ang1-7)] to promote biological pathways conducive to repair processes such as antisenescence (through the quantification of β-galactosidase and interleukin-6) and vasculogenesis (through the formation of endothelial tubes), demonstrated in vitro with human cardiac fibroblasts (hCFs) and human microvascular endothelial cells (hMECs), respectively. DPHI-NPs with a diameter of 190 ± 2 nm (polydispersity index < 0.2) and a zeta potential of −40 ± 1 mV were generated using an emulsion inversion technique and loaded with both therapeutic proteins (BMP-4 and Ang1-7) by optimizing surface charge, loading solution concentration, coating duration, and coating efficiency. Senescence-induced hCFs treated with functionalized DPHI-NPs were found to exhibit a significant reduction in expressed β-galactosidase and IL-6 ( p < 0.05). Additionally, hMECs treated with NP BMP-4 were found to display enhanced vasculogenesis compared to control culture conditions alone ( p < 0.05). The development of a DPHI-NP vector for the delivery of pro-regenerative secretome biomolecules may present an effective translatable strategy to improve their therapeutic efficacy with respect to cell function.
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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 | 0.001 | 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