Rational Design and Development of Dual location Dual Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery
Bibliographic record
Abstract
Design and development of smart nano-sized delivery devices for controlled drug release in response to endogenous stimuli (such as acidic pH and glutathione (GSH)) inherently found in tumor tissue is a promising platform in tumor-targeting nanomedicine. This platform allows for the maximization of therapeutic efficacy whilst reducing unwanted off-target side effects. Particularly, polymeric nanocarriers self-assembled from amphiphilic block copolymers (ABCP) have gained significant attention due of their size tunability and enhanced colloidal stability. Well-controlled ABCPs enable the formation of core-shell micelles in aqueous solutions having hydrophobic cores, enabling the physical entrapment of hydrophobic anticancer drugs, surrounded with hydrophilic coronas. Further, an incorporation of stimuli-responsive degradable (SRD) linkages in ABCPs allows for controlled micelle degradation and drug release at the site of action. \nIn this research, a dual location dual stimuli-responsive degradation (DL-DSRD) strategy is explored as a versatile platform for intracellular tumor-targeting drug delivery. Two ABCPs exhibiting dual acidic pH/reduction-responsive degradation are studied. The self-assembled ABCPs form colloidally stable nanoassemblies showing synergistically rapid release of encapsulated doxorubicin (a clinically used anticancer drug) at pH = 5.4 in 10 mM GSH solution caused by the cleavage of acid-labile and disulfide linkages. In addition, a new approach utilizing carbonylimidazole-hydroxyl coupling chemistry is explored to synthesize reduction-degradable poly(carbonate-disulfides) labeled with disulfide linkage on the backbones. They possess multi-functionalities as well as tunable and rapid reductive-degradation through main-chain degradation mechanism. Further, the versatility of the approach is demonstrated with the synthesis of an amphiphilic triblock copolymer exhibiting DL-DSRD responses. \nOverall, the results obtained through this research contribute to the advancement of current understanding and helps guide the design of improved SRD-exhibiting ABCP-based drug delivery nanocarriers.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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 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".