Developing Multifunctional Fe3O4@Au@pNIPAm Nanoparticles as Novel Theranostics

Abstract

Theranostics are nanodevices with diagnostic, therapeutic and possibly treatment-monitoring functions for treating cancers. Combining magnetic and plasmonic properties of nanoparticles (NPs) may provide new, high performance theranostics for millions of cancer patients and hence has provided a strong impetus for developing novel, multifunctional NPs. Fe3O4 NPs, owing to their magnetic property, have found medical applications such as magnetic resonance imaging and hyperthermia therapy for cancers. Au NPs are also attractive due to their high surface-enhanced Raman scattering (SERS), which can be used for high-sensitivity biodetection and photothermal ablation of cancer cells. Therefore, synthesizing hybrid NPs of Au and Fe3O4 can provide new platforms for developing novel theranostics. In the present study, a facile approach was developed to fabricate core-shell structured Fe3O4@Au NPs, which had a high efficiency for producing Fe3O4@Au NPs with desired size and shape in order to achieve the optimal optical property arising from the Au shell and the magnetic property due to the Fe3O4 core. After synthesizing Fe3O4@Au NPs, a coating of thermo-sensitive polymer poly(N-isopropylacrylamide) (pNIPAm) which was incorporated with anti-cancer drug 5-FU and the Raman reporter 4-MBA was produced on the NPs, forming multifunctional Fe3O4@Au@pNIPAm nanoparticles as a new type of theranostics. Owing to SERS, Fe3O4@Au@pNIPAm NPs could provide greatly amplified Raman signals, making them as highly desirable SERS tags in medical imaging for cancer detection. HRTEM images showed the formation of Au shell on Fe3O4 core. STEM mapping of Au and Fe and EDX analysis of Fe3O4@Au@pNIPAm NPs revealed the existence of Au and Fe in NPs. UV-Vis spectroscopy exhibited an SPR peak at 530 nm for Fe3O4@Au@pNIPAm NPs, suggesting the NPs had an equivalent Au NP diameter of 10 nm. DSC analysis of NPs indicated a lower critical solution temperature (LCST) of 32.3°C owing to the pNIPAm coating, and TGA results showed that the NPs contained 42.7 wt.% of pNIPAm. In vitro drug release studies were also conducted. At 30°C (below LCST), only a small amount (6.4%) of loaded 5-FU was released from Fe3O4@Au@pNIPAm NPs within 48 hr. At 42 °C (above LCST), 5-FU was released quickly from the NPs in the initial 6 hr and the release reached 83.1% within 48 hr. Fe3O4@Au@pNIPAm NPs with the attached anti-HER2 antibody could target SK-BR-3 cancer cells. In the presence of a magnetic field or NIR irradiation, there was a significant decrease in cell viability for SK-BR-3 cells incubated with 5-FU-loaded NPs because of combined hyperthermia therapy and photothermally guided drug delivery. Drug-loaded Fe3O4@Au@pNIPAm NPs are therefore multifunctional and have emerged as a novel theranostics.