Encapsulating a Hydrophilic Chemotherapeutic into Rod-like Nanoparticles of a Genetically Encoded Asymmetric Triblock Polypeptide Improves its Efficacy.


Journal Article

Encapsulating hydrophilic chemotherapeutics into the core of polymeric nanoparticles can improve their therapeutic efficacy by increasing their plasma half-life, tumor accumulation and intracellular uptake, and by protecting them from premature degradation. To achieve these goals, we designed a recombinant asymmetric triblock polypeptide (ATBP) that self-assembles into rod-shaped nanoparticles, and which can be used to conjugate diverse hydrophilic molecules, including chemotherapeutics, into their core. These ATBPs consist of three segments: a biodegradable elastin-like polypeptide, a hydrophobic Tyrosine-rich segment, and a short Cysteine-rich segment, that spontaneously self-assemble into rod-shaped micelles. Covalent conjugation of a structurally diverse set of hydrophilic small molecules, including a hydrophilic chemotherapeutic -gemcitabine- to the Cysteine residues also leads to formation of nanoparticles over a range of ATBP concentrations. Gemcitabine-loaded ATBP nanoparticles have significantly better tumor regression compared to free drug in a murine cancer model. This simple strategy of encapsulation of hydrophilic small molecules by conjugation to an ATBP can be used to effectively deliver a range of water-soluble drugs and imaging agents in vivo.

Full Text

Duke Authors

Cited Authors

  • Bhattacharyya, J; Weitzhandler, I; Ho, SB; McDaniel, JR; Li, X; Tang, L; Liu, J; Dewhirst, M; Chilkoti, A

Published Date

  • March 24, 2017

Published In

Volume / Issue

  • 27 / 12

PubMed ID

  • 30319320

Pubmed Central ID

  • 30319320

International Standard Serial Number (ISSN)

  • 1616-301X

Digital Object Identifier (DOI)

  • 10.1002/adfm.201605421


  • eng

Conference Location

  • Germany