Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer

Biomaterials. 2015 Jan;39:23-30. doi: 10.1016/j.biomaterials.2014.10.069. Epub 2014 Nov 15.

Abstract

Antibody-mediated therapies including antibody-drug conjugates (ADCs) have shown much potential in cancer treatment by tumor-targeted delivery of cytotoxic drugs. However, there is a limitation of payloads that can be delivered by ADCs. Integration of antibodies to drug-loaded nanocarriers broadens the applicability of antibodies to a wide range of therapeutics. Herein, we developed antibody fragment-installed polymeric micelles via maleimide-thiol conjugation for selectively delivering platinum drugs to pancreatic tumors. By tailoring the surface density of maleimide on the micelles, one tissue factor (TF)-targeting Fab' was conjugated to each carrier. Fab'-installed platinum-loaded micelles exhibited more than 15-fold increased cellular binding within 1 h and rapid cellular internalization compared to non-targeted micelles, leading to superior in vitro cytotoxicity. In vivo, Fab'-installed micelles significantly suppressed the growth of pancreatic tumor xenografts for more than 40 days, outperforming non-targeted micelles and free drugs. These results indicate the potential of Fab'-installed polymeric micelles for efficient drug delivery to solid tumors.

Keywords: Chemotherapy; Drug delivery; Micelle; Nanoparticle; Platinum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Humans
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fragments / chemistry*
  • Mice
  • Micelles*
  • Microscopy, Confocal
  • Nanoparticles / chemistry*
  • Pancreatic Neoplasms / drug therapy*
  • Platinum / chemistry*
  • Platinum / therapeutic use*
  • Polymers / chemistry*

Substances

  • Antineoplastic Agents
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Fragments
  • Micelles
  • Polymers
  • Platinum