Targeting the Tumor Core: Hypoxia-Responsive Nanoparticles for the Delivery of Chemotherapy to Pancreatic Tumors
| Autor: | Matthew Confeld, Michael A. Hollingsworth, Sanku Mallik, James Froberg, Li Feng, Heather Jensen-Smith, Babak Mamnoon, Mohiuddin A. Quadir, Yongki Choi, Jiha Kim, Priyanka Ray |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Polymers Pharmaceutical Science Mice Nude Antineoplastic Agents 02 engineering and technology 030226 pharmacology & pharmacy Article Extracellular matrix 03 medical and health sciences Mice 0302 clinical medicine Stroma Cancer stem cell Pancreatic cancer Cell Line Tumor Drug Discovery Extracellular medicine Animals Humans Hypoxia Chemistry Hypoxia (medical) 021001 nanoscience & nanotechnology medicine.disease Desmoplasia Pancreatic Neoplasms Polymersome Cancer research Neoplastic Stem Cells Molecular Medicine Nanoparticles Female medicine.symptom 0210 nano-technology Carcinoma Pancreatic Ductal |
| Zdroj: | Mol Pharm |
| ISSN: | 1543-8392 |
| Popis: | In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to unencapsulated drugs. The polymersomes decreased tumor growth by nearly 250% and significantly increased necrosis within the tumors by 60% in mice compared to untreated controls. We anticipate that these polymer nanoparticles possess a considerable translational potential for delivering drugs to solid hypoxic tumors. |
| Databáze: | OpenAIRE |
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