Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic Tumors in Vivo

Biomacromolecules. 2016 Oct 10;17(10):3213-3221. doi: 10.1021/acs.biomac.6b00941. Epub 2016 Sep 21.

Abstract

The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on poly(methacrylic acid) were prepared and functionalized with the somatostatin analogue PTR86 as the targeting moiety, since somatostatin receptors are overexpressed in pancreatic cancer. The gamma emitter 67Ga was incorporated by chelation and allowed in vivo investigation of the pharmacokinetic properties of the nanoparticles using single photon emission computerized tomography (SPECT). The resulting engineered nanosystem was tested in a xenograph mouse model of human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of targeted SCPNs in the tumor is higher than that observed for nontargeted nanoparticles due to improved retention in this tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Animals
  • Cell Line, Tumor
  • Early Detection of Cancer
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Polymers / chemistry
  • Polymethacrylic Acids / administration & dosage
  • Polymethacrylic Acids / chemistry
  • Somatostatin / biosynthesis*
  • Somatostatin / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Polymers
  • Polymethacrylic Acids
  • polymethacrylic acid
  • Somatostatin