Combinatorial Intracellular Delivery Screening of Anticancer Drugs
| Autor: | Edoardo Scarpa, Diana Moreira Leite, Aroa Duro-Castano, Belen Sola-Barrado, Giuseppe Battaglia |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
Combination therapy media_common.quotation_subject Phosphorylcholine Pharmaceutical Science Settore BIO/11 - Biologia Molecolare Pharmacology Endocytosis combination therapy 03 medical and health sciences intracellular drug delivery 0302 clinical medicine Polymethacrylic Acids Settore BIO/13 - Biologia Applicata Cell Line Tumor Drug Discovery Pediatric glioma Antineoplastic Combined Chemotherapy Protocols Humans drug screening drug solubilization polymeric nanoparticles synergy analysis 030304 developmental biology media_common 0303 health sciences Drug Carriers Chemistry Drug Synergism Glioma Hydrogen-Ion Concentration 3. Good health Solubility Solubilization Settore CHIM/09 - Farmaceutico Tecnologico Applicativo 030220 oncology & carcinogenesis Polymersome Settore BIO/14 - Farmacologia Molecular Medicine Nanoparticles Drug Screening Assays Antitumor Intracellular |
| Zdroj: | Molecular Pharmaceutics |
| Popis: | Conventional drug solubilization strategies limit the understanding of the full potential of poorly water-soluble drugs during drug screening. Here, we propose a screening approach in which poorly water-soluble drugs are entrapped in poly(2-(methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylaminoethyl methacryate) (PMPC-PDPA) polymersomes (POs) to enhance drug solubility and facilitate intracellular delivery. By using a human pediatric glioma cell model, we demonstrated that PMPC-PDPA POs mediated intracellular delivery of cytotoxic and epigenetic drugs by receptor-mediated endocytosis. Additionally, when delivered in combination, drug-loaded PMPC-PDPA POs triggered both an enhanced drug efficacy and synergy compared to that of a conventional combinatorial screening. Hence, our comprehensive synergy analysis illustrates that our screening methodology, in which PMPC-PDPA POs are used for intracellular codelivery of drugs, allows us to identify potent synergistic profiles of anticancer drugs. |
| Databáze: | OpenAIRE |
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