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Author Notes:

Corresponding author: Dr. Lily Yang, Department of Surgery, Emory University School of Medicine, Clinic C, Room C-4088, 1365 C Clifton Road, NE, Atlanta, GA 30322. Telephone: 404-778-4269; Fax: 404-778-5530. E-mail address: Lyang02@emory.edu

We thank Dr. Keping Xie for providing the PANC02 mouse pancreatic cancer cell line and Dr. Yuan Kai for detection of uPAR level in tumors by immunofluorescence labeling.

Dr. Y. Andrew Wang is the President and Principal Scientist, and Dr. Hongyu Chen is a Senior Scientist at Ocean Nanotech, LLC., San Diego, CA. All other authors do not have any conflicts of interest.

Subjects:

Research Funding:

We also thank research funding supports from NIH/NCI, including U01CA151810 (Yang and Mao) and R01CA202846-01(Yang, Mao and Wang), SBIR Phase II Contract NO. HHSN261201200029C (Wang, Yang and Mao), and F32CA189633 (Bozeman), and the Nancy Panoz Endowed Chair Funds (Yang).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • Targeted theranostic nanoparticles
  • tumor penetration
  • intraperitoneal drug delivery
  • image-guided therapy
  • pancreatic cancer
  • PLASMINOGEN-ACTIVATOR RECEPTOR
  • GYNECOLOGIC-ONCOLOGY-GROUP
  • PHASE-I TRIAL
  • OVARIAN-CANCER
  • PANCREATIC-CANCER
  • CYTOREDUCTIVE SURGERY
  • THERAPY
  • CHEMOTHERAPY
  • EXPRESSION
  • CARCINOMATOSIS

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery

Tools:

Journal Title:

Theranostics

Volume:

Volume 7, Number 6

Publisher:

, Pages 1689-1704

Type of Work:

Article | Final Publisher PDF

Abstract:

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

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© Ivyspring International Publisher.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/).

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