Multi-objective optimization of tumor response to drug release from vasculature-bound nanoparticles
Bibliographic record
Abstract
The pharmacokinetics of nanoparticle-borne drugs targeting tumors depends critically on nanoparticle design. Empirical approaches to evaluate such designs in order to maximize treatment efficacy are time- and cost-intensive. We have recently proposed the use of computational modeling of nanoparticle-mediated drug delivery targeting tumor vasculature coupled with numerical optimization to pursue optimal nanoparticle targeting and tumor uptake. Here, we build upon these studies to evaluate the effect of tumor size on optimal nanoparticle design by considering a cohort of heterogeneously-sized tumor lesions, as would be clinically expected. The results indicate that smaller nanoparticles yield higher tumor targeting and lesion regression for larger-sized tumors. We then augment the nanoparticle design optimization problem by considering drug diffusivity, which yields a two-fold tumor size decrease compared to optimizing nanoparticles without this consideration. We quantify the tradeoff between tumor targeting and size decrease using bi-objective optimization, and generate five Pareto-optimal nanoparticle designs. The results provide a spectrum of treatment outcomes - considering tumor targeting vs. antitumor effect - with the goal to enable therapy customization based on clinical need. This approach could be extended to other nanoparticle-based cancer therapies, and support the development of personalized nanomedicine in the longer term.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".