PMID- 27462153 OWN - NLM STAT- MEDLINE DCOM- 20170220 LR - 20181202 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 11 DP - 2016 TI - Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer. PG - 3087-99 LID - 10.2147/IJN.S92722 [doi] AB - 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. FAU - Huang, Jing AU - Huang J AD - Department of Radiology and Imaging Sciences; Center for Systems Imaging. FAU - Qian, Weiping AU - Qian W AD - Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA. FAU - Wang, Liya AU - Wang L AD - Department of Radiology and Imaging Sciences; Center for Systems Imaging. FAU - Wu, Hui AU - Wu H AD - Department of Radiology and Imaging Sciences. FAU - Zhou, Hongyu AU - Zhou H AD - Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA. FAU - Wang, Andrew Yongqiang AU - Wang AY AD - Ocean Nanotech LLC, Springdale, AR, USA. FAU - Chen, Hongbo AU - Chen H AD - School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, Guangxi, People's Republic of China. FAU - Yang, Lily AU - Yang L AD - Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA. FAU - Mao, Hui AU - Mao H AD - Department of Radiology and Imaging Sciences; Center for Systems Imaging. LA - eng GR - R01 CA154846/CA/NCI NIH HHS/United States GR - U01 CA151810/CA/NCI NIH HHS/United States GR - U01 CA198913/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20160707 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Antineoplastic Agents) RN - 0 (Drug Carriers) RN - 0 (Ferric Compounds) RN - 0 (Magnetite Nanoparticles) RN - 0 (Milk Proteins) RN - 1K09F3G675 (ferric oxide) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Animals MH - Antineoplastic Agents/*administration & dosage/chemistry MH - Cell Line, Tumor MH - Cisplatin/administration & dosage/therapeutic use MH - Drug Carriers/administration & dosage/adverse effects MH - Female MH - Ferric Compounds/chemistry MH - Humans MH - Magnetic Resonance Imaging/methods MH - Magnetite Nanoparticles/*administration & dosage/chemistry MH - Mice, Nude MH - Milk Proteins/*chemistry MH - Pancreatic Neoplasms/*diagnostic imaging/*drug therapy/pathology MH - Urokinase-Type Plasminogen Activator/administration & dosage/chemistry MH - Xenograft Model Antitumor Assays PMC - PMC4939990 OTO - NOTNLM OT - active targeting OT - cisplatin OT - drug delivery OT - magnetic nanoparticles OT - magnetic resonance imaging OT - pancreatic cancer EDAT- 2016/07/28 06:00 MHDA- 2017/05/26 06:00 PMCR- 2016/07/07 CRDT- 2016/07/28 06:00 PHST- 2016/07/28 06:00 [entrez] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/05/26 06:00 [medline] PHST- 2016/07/07 00:00 [pmc-release] AID - ijn-11-3087 [pii] AID - 10.2147/IJN.S92722 [doi] PST - epublish SO - Int J Nanomedicine. 2016 Jul 7;11:3087-99. doi: 10.2147/IJN.S92722. eCollection 2016.