Bibliographic record
Abstract
Texaphyrins are expanded porphyrin macrocycles with a 5-coordination pocket that can form stable 1:1 complexes with a large group of metal cations including many lanthanide ions, making them inherently amenable for theranostics (e.g., photodynamic therapy, MRI and radiation therapy). For example, gadolinium-texaphyrin (Gd-Tex, Xcytrin®) developed by the Sessler group was evaluated as a radiosensitizer all the way to Phase III trials. Although Gd-Tex did not gain FDA approval due to its limited radiosensitization efficacy, the fact that Gd-Tex showed good safety profile in phase III clinical trials makes texaphyrins attractive building block to develop new theranostic agents. We recently synthesized a texaphyrin-phospholipid building block via a key 1,2-dinitrophenyl-phospholipid intermediate, along with stable chelation of a library of 18 different metal ions into texaphyrin-lipid without compromising their self-assembly into nanotexaphyrins. To realize nanotexaphyrin’s theranostic properties, we developed a customizable strategy to build a family of nanotexaphyrins with quantitatively mixed and matched metal ions. We also developed a rapid and robust nanotexaphyrin radiolabeling method using a home-made disposable microfluidic system that achieved a high radiochemical yield. The optimized metalated nanotexaphyrin displayed excellent chemical, photo, and colloidal stabilities, and favorable pharmacokinetics and biodistribution profiles, resulting versatile cancer imaging and therapy applications. For example, the PSMA-targeted 111In/Lu-nanotexaphyrin demonstrated a preferential tumor accumulation in PSMA-positive tumor by both NIR fluorescence and SPECT/CT imaging, and a potent PDT effect that successfully inhibited PSMA+ tumor growth. On the radiation therapy front, we developed Gd-nanotexaphyrin to allow high density packing of Gd-Tex in a single nanovesicle to overcome the limited radiosensitization efficacy of monomeric Gd-Tex. As hypoxia is a common cause of radiation resistance, we loaded oxygen-carrying myoglobin into Gd-nanotexaphyrins, which enabled spatiotemporal codelivery of O2 and Gd-Tex into tumors, resulting in efficient relief of tumor hypoxia and significant enhancement of Gd-Tex radiosensitization. The synergistic mechanism between appropriate O2 delivery and enhanced Gd-Tex radiosensitization has been demonstrated. The high versatility and clinical translatability of nanotexaphyrins is a promising platform to develop cancer theranostics.
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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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".