Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20 + B-cell lymphoma

Wendy K. Nevala, John T. Butterfield, Shari L. Sutor, Daniel J. Knauer, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

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Abstract

We developed a nano-antibody targeted chemotherapy (nATC) delivery strategy in which tumor specific and clinically relevant antibodies (rituximab, anti-CD20) are non-covalently bound to the albumin scaffold of nab-paclitaxel (ABX). We define the nanoparticle formed when the 2 drugs are bound (AR160). The newly created nATC retains the cytotoxicity of ABX and CD20 affinity of rituximab in vitro. We describe the binding characteristics of the ABX and rituximab in AR160 using peptide mapping/Biacore approach. Flow-based methods, including ImageStream and nanoparticle tracking, were used to characterize the AR160 particles in vitro. A mouse model of human B-cell lymphoma was utilized to test in vivo efficacy of AR160 therapy, which suggested improved tumor targeting (biodistribution) as the most likely mechanism of AR160 therapeutic superiority over ABX or rituximab alone. These data suggest a novel platform for nATC delivery using a slight modification of existing cancer drugs with significantly improved treatment efficacy.

Original languageEnglish (US)
Article number45682
JournalScientific Reports
Volume7
DOIs
StatePublished - Apr 5 2017

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B-Cell Lymphoma
Paclitaxel
Nanoparticles
Antibodies
Drug Therapy
Neoplasms
Peptide Mapping
Therapeutics
Pharmaceutical Preparations
Albumins
Rituximab
In Vitro Techniques

ASJC Scopus subject areas

  • General

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Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20 + B-cell lymphoma. / Nevala, Wendy K.; Butterfield, John T.; Sutor, Shari L.; Knauer, Daniel J.; Markovic, Svetomir Nenad.

In: Scientific Reports, Vol. 7, 45682, 05.04.2017.

Research output: Contribution to journalArticle

Nevala, Wendy K. ; Butterfield, John T. ; Sutor, Shari L. ; Knauer, Daniel J. ; Markovic, Svetomir Nenad. / Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20 + B-cell lymphoma. In: Scientific Reports. 2017 ; Vol. 7.
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