Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer

• Type of Material: Article
• Authors: Jing Huang, Emory University; Wei Qian, Emory University; Liya Wang, Emory University; Hui Wu, Emory University; Hongyu Zhou, Emory Univ; Andrew Yongqiang Wang, Ocean Nanotech LLC; Hongbo Chen, Guilin Univ Elect Technol; Lily Yang, Emory University; Hui Mao, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: Dove Medical Press
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Huang et al.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2147/IJN.S92722
• Title of Journal or Parent Work: International Journal of Nanomedicine
• ISSN: 1176-9114
• Volume: 11
• Start Page: 3087
• End Page: 3099
• Grant/Funding Information: This work is supported by NIH R01CA154846-02 (HM and LY), NCI’s Cancer Nanotechnology Platform Project (CNPP) grant (U01CA151810-02 to LY and HM) and Emory Molecular Translational Imaging Center of NCI’s in vivo Cellular and Molecular Imaging Center grant (ICMIC, P50CA128301-01A10003 to HM and LY).
• Keywords: CISPLATIN NANOPARTICLES; GEMCITABINE; Pharmacology & Pharmacy; drug delivery; magnetic resonance imaging; magnetic nanoparticles; Science & Technology - Other Topics; pancreatic cancer; NAB-PACLITAXEL; Science & Technology; POLYMERIC MICELLES; Life Sciences & Biomedicine; IRON-OXIDE NANOPARTICLES; NANOMEDICINE; DRUG-DELIVERY; cisplatin; INACTIVATION; ACCUMULATION; Nanoscience & Nanotechnology; TUMORS; active targeting
• Research Categories: Health Sciences, Oncology; Physics, Radiation; Health Sciences, Medicine and Surgery

Abstract

Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein)-coated magnetic iron oxide (CNIO) nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF) of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP) were engineered on this nanoplatform. High drug loading (~25 wt%) and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that ATF-CNIO-CDDP can be an effective theranostic platform for active targeting-enhanced and image-guided cancer treatment while simultaneously reducing the systemic toxicity.