期刊
MOLECULAR PHARMACEUTICS
卷 17, 期 12, 页码 4709-4714出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c00791
关键词
drug screening; combination therapy; polymeric nanoparticles; drug solubilization; intracellular drug delivery; synergy analysis
资金
- ERC [MEViC 278793, CheSSTaG 769798]
- EPSRC/BTG Healthcare Partnership [EP/I00 1697/1]
- EPSRC Established Career Fellowship [EP/N026322/1]
- Children with Cancer UK [16-227]
- EPSRC/SomaNautix Healthcare Partnership [EP/R024723/1]
- EPSRC [EP/R024723/1, EP/N026322/1, EP/I001697/1] Funding Source: UKRI
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.
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