The Effects of Particle Size and Molecular Targeting on the Intratumoral and Subcellular Distribution of Polymeric Nanoparticles
Why this work is in the frame
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Bibliographic record
Abstract
The current study describes the impact of particle size and/or molecular targeting (epidermal growth factor, EGF) on the in vivo transport of block copolymer micelles (BCMs) in athymic mice bearing human breast cancer xenografts that express differential levels of EGF receptors (EGFR). BCMs with diameters of 25 nm (BCM-25) and 60 nm (BCM-60) were labeled with indium-111 ((111)In) or a fluorescent probe to provide a quantitative and qualitative means of evaluating their whole body, intratumoral, and subcellular distributions. BCM-25 was found to clear rapidly from the plasma compared to BCM-60, leading to an almost 2-fold decrease in their total tumor accumulation. However, the tumoral clearance of BCM-25 was delayed through EGF functionalization, enabling the targeted BCM-25 (T-BCM-25) to achieve a comparable level of total tumor deposition as the nontargeted BCM-60 (NT-BCM-60). Confocal fluorescence microscopy combined with MATLAB analyses revealed that NT-BCM-25 diffuses further away from the blood vessels (D(mean) = 42 +/- 9 microm) following extravasation, compared to NT-BCM-60 which mainly remains in the perivascular regions (D(mean) = 23 +/- 4 microm). The introduction of molecular targeting imposes the "binding site barrier" effect, which retards the tumor penetration of T-BCM-25 (D(mean) = 29 +/- 7 microm, p < 0.05). The intrinsic nuclear translocation property of EGF/EGFR leads to a significant increase in the nuclear uptake of T-BCM-25 in vitro and in vivo via active transport. Overall, these results highlight the need to consider multiple design parameters in the development of nanosystems for delivery of anticancer agents.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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