Imiquimod‐Loaded Phospholipid‐Free Small Unilamellar Vesicles Activate the Tumor Immune Microenvironment to Treat Liver Cancer and Liver Metastases
Bibliographic record
Abstract
Liver cancers are often diagnosed at advanced stages and are the fourth leading cause of cancer death globally. Liver metastases, particularly from colorectal cancer, occur in 66% of patients. Immunotherapies for these cancers are limited by immunosuppressive tumor microenvironments. To address this, phospholipid-free small unilamellar vesicles (PFSUV) are developed to deliver the toll-like receptor 7 agonist Imiquimod (IMQ) to hepatocytes. PFSUV consists of 83 mol% cholesterol and 17 mol% Tween80, with IMQ encapsulated in these 75-nm particles. Intravenous administration of PFSUV-IMQ sustained liver IFN-α levels over 24 h while reducing systemic exposure. In a CT26 liver metastasis model, PFSUV-IMQ combined with Oxaliplatin reduced tumor size, increased CD8+ T cell infiltration, and enhanced tumor apoptosis. In an HCA-1 liver cancer model, the same treatment decreased tumor burden, increased apoptosis, and reduced lung metastases. Flow cytometry revealed increased CD86+/MHC-II+ dendritic cells and IFN-γ+ CD8+ T cells in treated tumors. RNA-seq shows enrichment of innate immune activation genes after a single dose. These findings suggest that targeted IMQ delivery activates the tumor immune microenvironment, leading to reduced tumor burden in liver cancer and metastasis models.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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 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".