Attachment Triggered Self-Assembly of Drugs into Nanoparticles

We have explored the capacity of ELPs to self-assemble into nanostructures in response to a range of stimuli. In one example, we designed a chimeric polypeptide that consists of two segments: (VPGXG)n repeats followed by a short (GGY)n segment, and showed that attachment of multiple copies of a hydrophobic molecule at the Y position can impart sufficient amphiphilicity to the polypeptide and thereby drive its self-assembly into near-monodisperse nanoparticles with the attached hydrophobic small molecule embedded in the core of the nanoparticle. This is an interesting finding, because it appears that any molecule with a hydrophobicity that is greater than a threshold value appears to drive attachment-triggered self-assembly of the chimeric polypeptide into a nanoparticle. Because many cancer chemotherapeutics are insoluble hydrophobic small molecules with poor bioavailability, this approach of attachment-triggered encapsulation of small hydrophobic molecules into soluble nanoparticles has great utility to increase the solubility, plasma-half-life and tumor accumulation of cancer chemotherapeutics.


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