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The development, characterization and in vivo anti-ovarian cancer activity of poly(propylene imine) (PPI)-antibody conjugates containing encapsulated paclitaxel.

Abstract
Mesothelin, protein is frequently expressed in ovarian cancers. However, a full understanding of the biological functions of mesothelin is lacking. Here, we investigate the drug targeting potential of antibody conjugated modified half-generation poly (propylene imine) dendrimers i.e. immunodendrimers toward ovarian cancer with a model anti-cancer agent, paclitaxel (PTX). The synthesized plain 4.5G dendrimers as well as immunodendrimers were characterized by FT-IR, (1)H-NMR, TEM, and flow cytometry. Immunodendrimers exhibited considerably reduced hemolytic-, hepato- and nephrotoxicity. MTT cytotoxicity, flow cytometry and cell morphology studies were conducted in OVACAR-3 and A-431 cell. We demonstrate that PTX loaded immunodendrimers reduced the tumor volume significantly. The biodistribution studies further confirmed the targeting efficiency and higher biodistribution of immunodendrimers into the mesothelin protein expressing ovarian cancer cells. The results concluded that the developed immunodendrimers have potential to deliver significantly higher amount of the bioactive and have improved therapeutic outcome.
AuthorsNarendra K Jain, Manoj S Tare, Vijay Mishra, Pushpendra K Tripathi
JournalNanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 11 Issue 1 Pg. 207-18 (Jan 2015) ISSN: 1549-9642 [Electronic] United States
PMID25262579 (Publication Type: Journal Article)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Dendrimers
  • Msln protein, mouse
  • Polypropylenes
  • poly(propyleneimine)
  • L-Lactate Dehydrogenase
  • Mesothelin
  • Paclitaxel
Topics
  • Animals
  • Antineoplastic Agents (chemistry)
  • Cell Line, Tumor
  • Dendrimers
  • Drug Delivery Systems
  • Female
  • Humans
  • L-Lactate Dehydrogenase (chemistry)
  • Magnetic Resonance Spectroscopy
  • Mesothelin
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Transmission
  • Nanomedicine (methods)
  • Neoplasm Transplantation
  • Ovarian Neoplasms (drug therapy)
  • Paclitaxel (administration & dosage, chemistry)
  • Polypropylenes (chemistry)
  • Spectroscopy, Fourier Transform Infrared
  • Surface Properties

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