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Quantitative Self-Assembly Prediction Yields Targeted Nanomedicines
Development of targeted nanoparticle drug carriers often requires complex synthetic schemes involving both supramolecular self-assembly and chemical modification. Until recently, these processes were generally difficult to predict, execute, and control. We describe herein a targeted drug delivery sy...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930166/ https://www.ncbi.nlm.nih.gov/pubmed/29403054 http://dx.doi.org/10.1038/s41563-017-0007-z |
Sumario: | Development of targeted nanoparticle drug carriers often requires complex synthetic schemes involving both supramolecular self-assembly and chemical modification. Until recently, these processes were generally difficult to predict, execute, and control. We describe herein a targeted drug delivery system which is accurately and quantitatively predicted to self-assemble into nanoparticles based on the molecular structures of precursor molecules, which are the drugs themselves. The drugs assemble with the aid of sulfated indocyanines into particles with ultra-high drug loadings of up to 90%. Using quantitative structure-nanoparticle assembly prediction (QSNAP) calculations, we identified and validated electrotopological molecular descriptors as highly predictive indicators of nano-assembly and nanoparticle size. The resulting nanoparticles selectively targeted kinase inhibitors to caveolin-1-expressing human colon cancer and autochthonous liver cancer models to yield striking therapeutic effects while avoiding pERK inhibition in healthy skin. This finding enables a computational design of nanomedicines based on quantitative models for drug payload selection. |
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