Development of Itaconate Polymers Microparticles for Intracellular Regulation of Pro‐Inflammatory Macrophage Activation
Bibliographic record
Abstract
Abstract Itaconate (IA) is an endogenous metabolite and a potent regulator of the innate immune system. It's use in immunomodulatory therapies has faced limitations due to challenges in controlled delivery and requirements of high extracellular concentrations for internalization of the highly polar small molecule to achieve its intracellular therapeutic activity. Microparticle (MP)‐based delivery strategies are a promising approach for intracellular delivery of small molecule metabolites through macrophage phagocytosis and subsequent intracellular polymer degradation‐based delivery. Toward the goal of intracellular delivery of IA, degradable polyester polymer‐ (poly(dodecyl itaconate)) based IA polymer microparticles (IA‐MPs) are generated using an emulsion method, forming micron‐scale (≈1.5 µm) degradable microspheres. IA‐MPs are characterized with respect to their material properties and IA release kinetics to inform particle fabrication. Treatment of murine bone marrow‐derived macrophages with an optimized particle concentration of 0.1 mg million −1 cells enables phagocytosis‐mediated internalization and low levels of cytotoxicity. Flow cytometry demonstrates IA‐MP‐specific regulation of IA‐sensitive inflammatory targets. Metabolic analyses demonstrate that IA‐MP internalization inhibits oxidative metabolism and induced glycolytic reliance, consistent with the established mechanism of IA‐associated inhibition of succinate dehydrogenase. This development of IA‐based polymer microparticles provides a basis for additional innovative metabolite‐based microparticle drug delivery systems for the treatment of inflammatory disease.
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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) | 0.000 | 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 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".