Part 1

Multimodal nanoparticle based MRI-optical tracer systems for pancreastumor imaging and drug delivery in cell tissue and animal models

Oula Penate-Medina and Holger Kalthoff

Liposomes and micelles are common nanostructures in clinical use for drugdelivery. By preferentially enhancing localization of pharmaceutical activity to the organ/tissue of interest, their use may lead to reductions in the required dosage of drug, thus minimizing risks of systemic toxicity while increasing treatment efficacy.

There is ongoing research to improve the drug delivery by introducing targeted or functional delivery systems. New nanoparticle and smart drug delivery agents are needed for imaging and delivery approaches. However there has been clear lack of probes that can be used simultaneously in molecular and organ level and that can bring light to the back ground accumulation (EPR) and specific target-mediated uptake. Multimodal imaging agents are needed for molecular imaging because only optical reporters are versatile enough to be used in cellular imaging and microscopy but these tracers cannot be used efficiently in animal imaging because the quenching and quantification problems in the animal settings and the lack of anatomical data in optical imaging systems.

Here we describe a multimodal MRI-optical tracer system that is promising due to the fact that they can give the anatomical information in tissue and organ level inanimal models and in the same time give the precise information of the receptors and binding in cellular level. Our optical-MRI probe is based on liposomal 20nm iron nanoparticle (Micromod) targeted with RA‐96 Fab2 against mucins and co-encapsulated optical Indocyanide green (ICG).

Part 2

Encoding the diversity between pancreatic head and body/tail cancers: the differential expression of miR-501-3p and miR-375

Qi Ling 1and Holger Kalthoff 2

1 Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery,First Affiliated Hospital, Zhejiang University, Hangzhou, China; 2 Institute for Experimental Cancer Research, Comprehensive Cancer Center North, UK S-H, Campus Kiel, Germany

ABSTRACT

Different clinical outcome has been found between pancreatic head cancer and pancreatic body/tail cancer. MicroRNAs have been reported to play potent functional roles in the complex functional pathway networks controlling important cellular processes including tumor progression and invasion. To identify miRNA signatures that may encode the difference, microarrays covering 887 human miRNAs in strictly matched early stage (I-II) pancreatic body/tail cancers andhead cancers were performed and the results were further verified by qRT-PCR.We found remarkably lower expression of miR-501-3p and higher expression of miR-375 in pancreatic body/tail cancer compared with head cancer. The recurrence rate was obviously lower in pancreatic body/tail cancer, and the low expression of miR-501-3p was significantly associated with low-risk of recurrence after curative surgery. In an in vitrostudy, miR-501-3p was found to promote invasion in both Panc-1 and colo357 cells possibly via regulating E- and VE-Cadherin. Furthermore, VE-cadherin was verified to be a direct target of miR-501-3p by dual-luciferase reporter assay.Our results suggest that pancreatic body/tail cancer is ‘less’ malignant than pancreatic head cancer and two miRNAs (miR-501-3p and -375) may encode the diversity.