Abstract B021: Multi-functional telodendrimer nanodrug: Nanocarrier for ovarian cancer treatment and immunomodulator to control inflammation and sensitize the tumor
Notice bibliographique
Résumé
Abstract Introduction: Inflammation plays a key role in all stages of ovarian cancer (OC), starting from tumorigenesis to progression and therapy resistance, till metastasis and recurrence. Toll-like receptors (TLRs) are pathogen-related receptors that initiate inflammatory responses. Pathogen-Associated Molecular Pattern (PAMPs), such as LPS released from pathogens, or DAMPs (Damage-Associated Molecular Pattern) released from dead cells, stimulate TLRs expressed on immune and OC cells. These stimulations activate signaling pathways such as NF-kB and STAT-3 to secrete pro-inflammatory protumor cytokines (e.g., IL-6), leading to tumor progression. Targeted therapy, such as PARP inhibitors (e.g., Olaparib), is used to treat OC patients. However, multiple resistance mechanisms have been attributed to Olaparib, including the activation of NF-kB and STAT3 oncogenic signaling. We have developed a library of immunomodulatory Telodendrimer (TD) nanoparticles that can also be used as drug delivery systems. Here, we speculate that dual-functional TD that acts as a TLR2/4 antagonist and a nanocarrier for Olaparib can control inflammation and the resulting tumor progression, as well as sensitize the tumor to Olaparib. Results and Methods: As an immunomodulator, TD specifically inhibits TLR2 and TLR4 activation using reporter HEK cells overexpressing TLR2 and TLR4, respectively. TD also inhibits TLR2/4 activation by DAMPs prepared via sonication of OC cells in these HEK cells and also inhibits the consequent proinflammatory cytokines (TNF-α and IL-6) secreted by THP-1 human differentiated macrophages using ELISA. In OC cell lines, TD suppresses IL-6 levels secreted in an autocrine manner, and when cells are stimulated with LPS (TLR4 agonist), DAMPs, and in immune-OC coculture using ELISA, by inhibiting NF-kB and STAT-3 phosphorylation shown by western blot. Consequently, it controls OC proliferation enhanced by LPS, LTA (TLR2 agonist), DAMPs, and the inflammatory secretome of macrophages (conditioned media of THP-1 differentiated macrophages stimulated with LPS) using MTS. Interestingly, TD directly impedes the migration of OC cells demonstrated by scratch assay. In vivo, TD alone restricts tumor progression in mice injected i.p. with ID8-luc OC cells, reflected by decreased bioluminescence signal. It also decreases the plasma levels of TNF-α and IL-6 in ID-8-luc OC bearing mice injected i.p. with LPS using ELISA. As a nanocarrier for Olaparib TD(OLA), the loading is characterized by studying the particle size and stability by dynamic light scattering (DLS) and the release profile by UV-Vis. TD(OLA) shows a small and stable particle size with sustained release compared to Olaparib alone. TD(OLA) preferentially sensitizes OC cells compared to Olaparib as monotherapy and in combination with TD. Conclusion: The dual function of TD as an immunomodulator and a nanocarrier for Olaparib can control the inflammation, inhibit tumor progression and migration, and sensitize OC cells to treatment. Citation Format: Hadil A. Gadelrab, Changying Shi, Dandan Guo, Rinki Agarwal, Sandra Orsulic, Juntao Luo. Multi-functional telodendrimer nanodrug: Nanocarrier for ovarian cancer treatment and immunomodulator to control inflammation and sensitize the tumor [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr B021.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».