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Author Notes:

Address correspondence to yang02@emory.edu.

We thank Dr. Erica N. Bozeman for editing the manuscript.

The authors declare no competing financial interest.

Subjects:

Research Funding:

This research project was supported by the NIH/NCI grants U01CA151810 (L.Y. and H.M.), R01 CA154129A1 (L.Y.), R01CA154846 (H.M. and L.Y.), NIH/NCI SBIR Contract No. HHSN261201200029C (Y.A.W. and L.Y.), U01-CA-151837 (F.M.U.), and R01-CA-154471 (F.M.U.), and by the Nancy Panoz Endowed Chair Funds (L.Y.).

Keywords:

  • Science & Technology
  • Physical Sciences
  • Technology
  • Chemistry, Multidisciplinary
  • Chemistry, Physical
  • Nanoscience & Nanotechnology
  • Materials Science, Multidisciplinary
  • Chemistry
  • Science & Technology - Other Topics
  • Materials Science
  • IGF1R-targeted cancer therapy
  • theranostic nanoparticles
  • orthotopic pancreatic cancer patient tissue derived xenografts
  • MRI
  • image-guided cancer therapy
  • GROWTH-FACTOR RECEPTOR
  • CELL LUNG-CANCER
  • PEGYLATED LIPOSOMAL DOXORUBICIN
  • FACTOR-I RECEPTOR
  • TUMOR XENOGRAFTS
  • DRUG-DELIVERY
  • ENHANCED PERMEABILITY
  • DUCTAL ADENOCARCINOMA
  • INSULIN
  • GEMCITABINE

IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer

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Journal Title:

ACS Nano

Volume:

Volume 9, Number 8

Publisher:

, Pages 7976-7991

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

Copyright information:

© 2015 American Chemical Society.

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