Efficient siRNA delivery and gene silencing using self-assembled rosette nanotubes
Bibliographic record
Abstract
Background: Self-assembly and self-organization processes offer a powerful strategy for the design of nanomaterials from the ground up with predefined dimensions and properties. Central to these approaches is the design and synthesis of molecules with a built-in ability to undergo a hierarchical sequence of supramolecular reactions, culminating with the formation of a well-defined functional superstructure. The rosette nanotubes (RNTs) are a new class of biocompatible organic nanomaterials with tunable dimensions and properties. They are obtained through the hierarchical self-assembly of small synthetic organic molecules. They can be readily tailored to target and kill cancerous cells. Objectives: Our aim is to address the following issues: (i) extent to which the RNTs can capture and deliver siRNA to a tumour while retaining their activity, (ii) advantages and/or limitations of RNTs compared to clinically tested drug delivery systems (DDS), (iii) effectiveness of RNT-based formulations in cancer treatment, (iv) specificity and real-time tracking of the RNT DDS, (v) toxicity profile of the new RNT DDS, (vi) identification of optimal cancer targets for the RNT DDS, and (vii) categorization of the therapeutic advantages/challenges of this system in animal models. Methods: We have designed a family of RNTs and characterized them chemically and structurally. We have also tested their ability to capture siRNA and deliver it to cancer cells. Results: The binding efficiency was shown to be a function of RNT/siRNA ratio, net charge, and local cationic density. These formulations were reproducible at different ionic strength media and were shown to protect siRNA from degradation by serum nucleases. Moreover, the presence of siRNA also played a role in dictating the supramolecular shape of the nanocarrier, which may reflect in-cell uptake and the resulting silencing process. Fluorescence microscopy showed that Caco-2 cells can take up RNT derived assemblies very readily within 4 hours and retain siRNA up to 72 hours. Silencing experiments showed a dose-dependent reduction in VEGF protein levels secreted by Caco-2 cells reaching approximately 40% reduction at 20 nM siRNA. Conclusions: We have shown that the RNTs are effective oligonucleotide carriers. Future studies will involve animal studies and further optimization of the observed therapeutic effect.
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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 | 0.000 |
| 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 | 0.001 |
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".