PLA‐Based Triblock Copolymer Micelles Exhibiting Dual Acidic pH/Reduction Responses at Dual Core and Core/Corona Interface Locations
Bibliographic record
Abstract
Polylactide (PLA)-based amphiphilic block copolymers and their nanoassemblies designed with stimuli-responsive degradation (SRD) hold great potential as promising candidates for tumor-targeting drug delivery. However, most of the smart PLA-based nanoassemblies are designed to respond to a single stimulus (typically reduction or acidic pH). Herein, a new strategy is reported to synthesize PLA-based block copolymer micelles exhibiting dual SRD at dual locations (DL-DSRD). The strategy utilizes a combination of ring opening polymerization, controlled radical polymerization, and facile coupling reactions to synthesize an ABA-type PLA-based triblock copolymer with a hydrophilic polymethacrylate (A) and PLA (B) blocks. Incorporation of an acidic pH-responsive ketal linkage in the center of PLA block and reduction-responsive disulfide linkages at PLA/hydrophilic polymethacrylate blocks ensure the formation of smart nanoassemblies featured with ketal linkages in the PLA cores and disulfide linkages at core/corona interfaces, thus attaining DL-DSRD. Such dual acidic pH/reduction-responses at dual locations lead to not only shedding of coronas at interfaces but also destabilization of cores, resulting in the synergistic and accelerated release of encapsulated model drugs, compared with the single stimulus systems. These results, along with lower cytotoxicity, suggest that DL-DSRD strategy can offer versatility in the development of tumor-targeting drug delivery nanocarriers.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".