Macrophage targeted cellular microparticles synergize anti-tuberculosis therapy combining CircRNA-mediated host immune defense and antibiotic killing
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
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the most deadly infectious diseases worldwide. There is an urgent need for the development of innovative strategies improving the antibiotic efficiency and enhancing host immunological defenses for more effective TB treatment. CircRNA TRAPPC6B (circTRAPPC6B) can enhance autophagy and M1 polarization of Mtb infected macrophages to facilitate intracellular Mtb clearance, arising the promise for more effective anti-TB treatment. Here, we innovated macrophage targeted cellular microparticles encapsulating circTRAPPC6B and rifampicin inside to synergize targeted drug killing and enhanced host immunological clearance, thereby providing more effective anti-TB treatment to optimize therapeutic outcomes. The engineered Gal-CircRNA@Rif@MPs nanosystem showed selective macrophage targeting effects due to galacose surface functionalization and could significantly increase intracellular circTRAPPC6B levels, thereby promoting autophagy and anti-bacterial polarization of Mtb infected macrophages. Collectively, Gal-CircRNA@Rif@MPs demonstrated enhanced intracellular Mtb killing efficiency by synergizing targeted rifampicin action and antibacterial host immune defenses, thus significantly reducing Mtb burdens and alleviating lung tissue pathology in Mtb-infected mice without notable toxicity. Our findings demonstrate, for the first time, that circRNAs with immunomodulatory properties can be effectively combined with anti-TB drugs using cellular microparticles to achieve host cell-targeted Mtb clearance with alleviated pathology and acceptable toxicity profiles. These results introduce the potentials of Gal-CircRNA@Rif@MPs as novel host cell targeted system to synchronize selective antibiotic actions and host immunological defenses for more effective anti-TB treatment, advancing novel therapeutics against TB . Fig.1 Scheme for the preparation of Gal-CircRNA@Rif@MPs and Gal-CircRNA@Rif@MPs-mediated anti-TB therapeutic by combining targeted drug killings, enhanced host cell autophagy/apoptosis and promoted M1 macrophage polarization for more effective anti-TB treatment (By Figdraw). • We innovated macrophage targeted cellular microparticles (Gal-CircRNA@Rif@MPs) encapsulating circTRAPPC6B and rifampicin inside. • Gal-CircRNA@Rif@MPs firstly introduced functional circRNA for anti-TB treatment. • Gal-CircRNA@Rif@MPs can synergize targeted drug killing and enhanced host immunological clearance for more effective TB treatment.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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