Targeted phase-change contrast agents for intracellular delivery to breast cancer tumors: An <i>In vitro</i> study in MDA-MB-231 breast cancer cells
Bibliographic record
Abstract
We have found that folate-targeted, ultrasound-activated phase-change contrast agents (PCCAs) composed of volatile perfluorocarbons are able to bind and internalize within breast cancer cells prior to vaporization into intracellular microbubbles. We here report studies assessing internalization, stability to thermal activation, and ultrasound activation of PCCAs formed by condensation of dodecafluoropentane (DDFP), decafluorobutane (DFB), and octafluoropropane (OFP). Using a Zonare “z.one-ultra” ultrasound system and L14-5sp probe operating in B-mode at 9 MHz (frame rate 13 Hz) to activate PCCAs and imaging with a Leica confocal microscope, we studied delivery in cultured MDA-MB-231 breast cancer cells with folate-targeted PCCAs. The number of internalized bubbles pre- and post- insonation were measured as a function of: 1) PCCA incubation times (i.e 10 mins, 60 mins); 2) ultrasound exposure (4 passes vs. 12 passes); and 3) mixtures of OFP, DFB, and DDFP. DFB:DDFP PCCAs, 60 minute incubations, and 12 passes offered a promising combination of stability and activation, with post-ultrasound to pre-ultrasound microbubble ratios approximating 3.4 (microbubbles pre-ultrasound per cell = 0.68 + /- 0.49, microbubbles post-ultrasound per cell = 2.35 + /- 0.79). Results indicate that intracellular delivery of targeted-PCCAs can potentially offer a new methodology for clinical application with ultrasound-mediated intracellular imaging of breast cancer.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.000 | 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 source (direct Gemma or distilled Codex), 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".