title: Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer.
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.
authors.affiliation: Department of Radiology and Imaging Sciences; Center for Systems Imaging.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Radiology and Imaging Sciences; Center for Systems Imaging.
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiology and Imaging Sciences.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Ocean Nanotech LLC, Springdale, AR, USA.
authors.forename: Andrew Yongqiang
authors.initials: AY
authors.lastname: Wang
authors.affiliation: School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, Guangxi, People's Republic of China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Radiology and Imaging Sciences; Center for Systems Imaging.
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008819:Mice, Nude; D008894:Milk Proteins / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D008894:Milk Proteins; C000499:ferric oxide; D014568:Urokinase-Type Plasminogen Activator; D002945:Cisplatin
keywords: active targeting; cisplatin; drug delivery; magnetic nanoparticles; magnetic resonance imaging; pancreatic cancer