publications by Ashutosh Chilkoti.


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Papers Published

  1. MacKay, JA; Chen, M; McDaniel, JR; Liu, W; Simnick, AJ; Chilkoti, A, Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection, Nature Materials, vol. 8 no. 12 (December, 2009), pp. 993-999, Nature Publishing Group [19898461], [doi] .
    (last updated on 2021/07/30)

    Abstract:
    New strategies to self-assemble biocompatible materials into nanoscale, drug-loaded packages with improved therapeutic efficacy are needed for nanomedicine. To address this need, we developed artificial recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into sub-100-nm-sized, near-monodisperse nanoparticles on conjugation of diverse hydrophobic molecules, including chemotherapeutics. These CPs consist of a biodegradable polypeptide that is attached to a short Cys-rich segment. Covalent modification of the Cys residues with a structurally diverse set of hydrophobic small molecules, including chemotherapeutics, leads to spontaneous formation of nanoparticles over a range of CP compositions and molecular weights. When used to deliver chemotherapeutics to a murine cancer model, CP nanoparticles have a fourfold higher maximum tolerated dose than free drug, and induce nearly complete tumour regression after a single dose. This simple strategy can promote co-assembly of drugs, imaging agents and targeting moieties into multifunctional nanomedicines.