A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models

Jayanta Bhattacharyya, Joseph J. Bellucci, Isaac Weitzhandler, Jonathan R. McDaniel, Ivan Spasojevic, Xinghai Li, Chao-Chieh Lin, Jen-Tsan Ashley Chi and Ashutosh Chilkoti ()
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Jayanta Bhattacharyya: Duke University
Joseph J. Bellucci: Duke University
Isaac Weitzhandler: Duke University
Jonathan R. McDaniel: Duke University
Ivan Spasojevic: Oncology, Duke University Medical Center
Xinghai Li: Duke University
Chao-Chieh Lin: Duke University Medical Center
Jen-Tsan Ashley Chi: Duke University Medical Center
Ashutosh Chilkoti: Duke University

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Packaging clinically relevant hydrophobic drugs into a self-assembled nanoparticle can improve their aqueous solubility, plasma half-life, tumour-specific uptake and therapeutic potential. To this end, here we conjugated paclitaxel (PTX) to recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into ∼60 nm near-monodisperse nanoparticles that increased the systemic exposure of PTX by sevenfold compared with free drug and twofold compared with the Food and Drug Administration-approved taxane nanoformulation (Abraxane). The tumour uptake of the CP–PTX nanoparticle was fivefold greater than free drug and twofold greater than Abraxane. In a murine cancer model of human triple-negative breast cancer and prostate cancer, CP–PTX induced near-complete tumour regression after a single dose in both tumour models, whereas at the same dose, no mice treated with Abraxane survived for >80 days (breast) and 60 days (prostate), respectively. These results show that a molecularly engineered nanoparticle with precisely engineered design features outperforms Abraxane, the current gold standard for PTX delivery.

Date: 2015
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DOI: 10.1038/ncomms8939

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