1. Combinatorial intracellular delivery screening of anticancer drugs
- Author
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Sola Barrado, María Belén
- Abstract
Conventional drug solubilisation strategies limit the understanding of the full potential of poorly water-soluble drugs during drug screening. Here, I propose a screening approach in which poorly water-soluble drugs are entrapped in poly (2- (methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylaminoethyl methacryate) (PMPC-PDPA) or Angiopep-2-poly(ethylene glycol)-PDPA (AP-PEG-PDPA) polymersomes (POs) to enhance drug solubility and facilitate intracellular delivery. By using a human paediatric glioma cell model, I demonstrated that PMPC-PDPA and AP-PEG-PDPA POs mediated intracellular delivery of cytotoxic and epigenetic drugs by receptor-mediate endocytosis. Additionally, when delivered in combination, drug-loaded PMPC-PDPA and AP-PEG-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 and AP-PEG-PDPA POs are used for intracellular co-delivery of drugs, allows us to identify potent synergistic profiles of anticancer drugs.
- Published
- 2021