Novel strategy for targeted photodynamic therapy of breast cancer using a chlorin e6 conjugated-aptamer
Bibliographic record
Abstract
C101 There is a pressing need to develop small probes and drugs able to target breast cancer cells. Such agents would greatly benefit the diagnosis and treatment of breast cancer in patients. Our laboratory has been developing short oligonucleotides termed aptamers (1) that target un-glycosylated and glycosylated forms (Tn antigen) of the well-known epithelial tumour marker mucin MUC1 (2). These aptamers were identified from an combinatorial DNA oligonucleotide library (diversity: 4e25 elements) using the SELEX approach (3,4) (Systematic Evolution of Ligands by EXponential enrichment) for their ability to bind to each of three synthetically defined, mucin MUC1 tumour markers. The affinity constants of several aptamers for their MUC1 targets were determined to be in the nanomolar range. These molecules were readily internalized by cells expressing these surface markers. More importantly, the cell targeting and intracellular routing of these aptamers were exploited by synthetically incorporating the photodynamic therapy agent chlorin e6 at their 5’end. The resulting aptamers were selective for cancer cells expressing deglycosylated or underglycosylated MUC1 forms and could be readily activated by light to kill such cells at nanomolar concentrations. Finally, we report that these chlorin e6 conjugated-aptamers are presently being evaluated as in vivo imaging agents and in causing the regression of human breast cancer xenografts (MCF-7 and T47D) implanted in nude mice. In summary, our findings suggest that cytotoxic DNA aptamers directed at aberrantly glycosylated mucin antigens may serve as potent anticancer therapeutics against most epithelial cancers [Supported by Canadian Breast Cancer Research Alliance in association with the Canadian Cancer Society] 1. E. N. Brody, L. Gold, Reviews in Molecular Biotechnology 74, 5 (2000). 2. R. D. Brokx et al. , Biochemistry 42, 13817 (2003). 3. S. J. Ellington AD, Nature 346, 818 (1990). 4. G. L. Tuerk C, Science 249, 505 (1990).
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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) | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".