Introduction Pancreatic cancer carries a poor prognosis despite improvement through the use of adjuvant chemotherapy. Nanotechnology offers the possibility for patient tailored therapy by providing novel methods of targeted drug delivery. Aim To develop a nanoparticle drug delivery vehicle capable of multi-modal targeted drug release Methods Hybrid nanoparticles (SpHyNs) were manufactured from superparamagnetic iron oxide cores and an amphiphilic polyoxazoline polymer shell using a self- assembly methodology. They were loaded with a gemcitabine prodrug, modified for release at low pH levels found in endosome. Multi-modal targeting using a cancer specific antibody and a focused magnetic field was assessed. Results SpHyNs were taken up into cells via endocytosis permitting use of a pH-dependent drug release mechanism. The cytotoxicity of targeted drug-laden SpHyNs was significantly increased against target positive cancer cells. Magnetically targeted drug release showed significant reduction in cell count at the area of greatest magnetic force. Conclusion We developed a superparamagnetic hybrid nanoparticle with multi-modal targeting capabilities and a novel drug-release mechanism. This could reduce off-target effects leading to increased chemotherapy agent efficacy and offer the prospect for new treatments in pancreatic cancer.