title: A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models.
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.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708-0281, USA.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Bhattacharyya
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708-0281, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Bellucci
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708-0281, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Weitzhandler
authors.affiliation: 1] Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708-0281, USA [2] Department of Chemical Engineering, Institute for Molecular and Cellular Biology, University of Texas at Austin, Austin, Texas 78712-1062, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: McDaniel
authors.affiliation: 1] Department of Medicine, Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Medicine, Pharmaceutical Research PK/PD Core Laboratory, Duke Cancer Institute, Durham, North Carolina 27710, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708-0281, USA.
authors.forename: Xinghai
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27708, USA [2] Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Chao-Chieh
authors.initials: CC
authors.lastname: Lin
authors.affiliation: 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27708, USA [2] Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Jen-Tsan Ashley
authors.initials: JT
authors.lastname: Chi
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708-0281, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000068196:Albumin-Bound Paclitaxel / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D058726:Nanoconjugates; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010455:Peptides; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000648:ultrastructure; D011994:Recombinant Proteins; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000648:ultrastructure; D023041:Xenograft Model Antitumor Assays
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000970:Antineoplastic Agents; D058726:Nanoconjugates; D010455:Peptides; D011994:Recombinant Proteins; D017239:Paclitaxel