Phytoglycogen-dsRNA nanoparticles demonstrate differential cytotoxicity and immunostimulatory potential in two ovarian cancer cell lines
Bibliographic record
Abstract
Abstract Background Ovarian cancer is a leading cause of cancer mortality in women, and only a small percentage of cases are caught at an early stage. Novel treatments with improved efficacy are needed to fight ovarian cancer and to overcome resistance to traditional therapies. Double-stranded (ds) RNA, including the synthetic polyinosinic cytidylic acid (poly (I:C), has shown promise as a cancer therapeutic. Two ovarian cancer cell lines were tested for their ability to produce an immune response to poly (I:C) delivered using a nanoparticle carrier, a biodegradable phytoglycogen derived from sweet corn, called nanodendrix (NDX). SKOV-3 and OVCAR-3 have been previously identified as dsRNA-resistant and dsRNA-sensitive, respectively. Results Firstly, NDX was found to effectively bind poly (I:C), at a w/w ratio of 2:1 NDX:poly (I:C), the resulting particles, poly (I:C)-NDX, were tested for biological activity through uptake and two therapeutic modes of action, cytotoxicity and stimulation of the innate immune response. Both cell lines bound poly (I:C)-NDX, as observed using immunocytochemistry. In OVCAR-3 poly (I:C)-NDX caused significant cell death, even at concentrations as low as 62.5ng/mL, measured using the cell viability indicator dye alamarBlue; no cell death was observed with poly (I:C) alone across all concentrations, up to 5µg/mL in SKOV-3 and 0.5µg/mL in OVCAR-3. In both OVCAR-3 and SKOV-3, poly (I:C)-NDX stimulated the production of an innate immune chemokine, CXCL10, at the transcript and protein levels, at significantly higher levels than poly (I:C) alone. Interestingly, in response to poly (I:C)-NDX SKOV-3 produced a more robust immune response compared and higher levels of capase-3/-7 activation compared to OVCAR-3, despite showing no significant cell death. Conclusions Poly (I:C)-NDX represents a robust and multifunctional therapy with demonstrated efficacy against a range of ovarian tumour cells, potentiating poly (I:C) and sensitizing resistant cells. Additionally, the SKOV-3 and OVCAR-3 combination represents a powerful comparative model to help unravel dsRNA-mediated immune responses in ovarian cancer cells.
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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) | 0.001 | 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".