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

Publication ,  Journal Article
Bhattacharyya, J; Bellucci, JJ; Weitzhandler, I; McDaniel, JR; Spasojevic, I; Li, X; Lin, C-C; Chi, J-TA; Chilkoti, A
Published in: Nat Commun
August 4, 2015

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 4, 2015

Volume

6

Start / End Page

7939

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Triple Negative Breast Neoplasms
  • Recombinant Proteins
  • Prostatic Neoplasms
  • Peptides
  • Paclitaxel
  • Neoplasm Transplantation
  • Nanoparticles
  • Nanoconjugates
  • Microscopy, Fluorescence
 

Citation

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Bhattacharyya, J., Bellucci, J. J., Weitzhandler, I., McDaniel, J. R., Spasojevic, I., Li, X., … Chilkoti, A. (2015). A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models. Nat Commun, 6, 7939. https://doi.org/10.1038/ncomms8939
Bhattacharyya, Jayanta, Joseph J. Bellucci, Isaac Weitzhandler, Jonathan R. McDaniel, Ivan Spasojevic, Xinghai Li, Chao-Chieh Lin, Jen-Tsan Ashley Chi, and Ashutosh Chilkoti. “A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models.Nat Commun 6 (August 4, 2015): 7939. https://doi.org/10.1038/ncomms8939.
Bhattacharyya J, Bellucci JJ, Weitzhandler I, McDaniel JR, Spasojevic I, Li X, et al. A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models. Nat Commun. 2015 Aug 4;6:7939.
Bhattacharyya, Jayanta, et al. “A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models.Nat Commun, vol. 6, Aug. 2015, p. 7939. Pubmed, doi:10.1038/ncomms8939.
Bhattacharyya J, Bellucci JJ, Weitzhandler I, McDaniel JR, Spasojevic I, Li X, Lin C-C, Chi J-TA, Chilkoti A. A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models. Nat Commun. 2015 Aug 4;6:7939.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 4, 2015

Volume

6

Start / End Page

7939

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Triple Negative Breast Neoplasms
  • Recombinant Proteins
  • Prostatic Neoplasms
  • Peptides
  • Paclitaxel
  • Neoplasm Transplantation
  • Nanoparticles
  • Nanoconjugates
  • Microscopy, Fluorescence