Metastatic oral squamous cell carcinoma (SCC) displays a poor disease prognosis with a 5-year survival rate of 39%. Chemotherapy has emerged as the mainstream treatment against small clusters of cancer cells but poses more risks than benefits for metastatic cells due to the non-specificity and cytotoxicity. To overcome these obstacles, we conjugated antibodies specific for matrix metalloproteinase-1 (MMP-1), a prognostic biomarker of SCC, to iron–gold bimetallic nanoparticles (FeAu NPs) and explored the capability of this complex to target and limit SSC cell growth via magnetic field-induced hyperthermia. Our results showed that 4.32 ± 0.79 nm sized FeAu NPs were superparamagnetic in nature with a saturation magnetization (Ms) of 5.8 emu/g and elevated the media temperature to 45 °C, confirming the prospect to deliver hyperthermia. Furthermore, conjugation with MMP-1 antibodies resulted in a 3.07-fold higher uptake in HSC-3 (human tongue squamous cell carcinoma) cells as compared to L929 (fibroblast) cells, which translated to a 5-fold decrease in cell viability, confirming SCC targeting. Finally, upon magnetic stimulation, MMP-1-FeAu NPs conjugate triggered 89% HSC-3 cellular death, confirming the efficacy of antibody-conjugated nanoparticles in limiting SCC growth. The synergistic effect of biomarker-specific antibodies and magnetic nanoparticle-induced hyperthermia may open new doors towards SCC targeting for improved disease prognosis.
The interactions between cells and nanomaterials at the nanoscale play a pivotal role in controlling cellular behavior and ample evidence links cell intercommunication to nanomaterial size. However, little is known about the effect of nanomaterial geometry on cell behavior. To elucidate this and to extend the application in cancer theranostics, we have engineered core–shell cobalt–gold nanoparticles with spherical (Co@Au NPs) and elliptical morphology (Co@Au NEs). Our results show that owing to superparamagnetism, Co@Au NPs can generate hyperthermia upon magnetic field stimulation. In contrast, due to the geometric difference, Co@Au NEs can be optically excited to generate hyperthermia upon photostimulation and elevate the medium temperature to 45 °C. Both nanomaterial geometries can be employed as prospective contrast agents; however, at identical concentration, Co@Au NPs exhibited 4-fold higher cytotoxicity to L929 fibroblasts as compared to Co@Au NEs, confirming the effect of nanomaterial geometry on cell fate. Furthermore, photostimulation-generated hyperthermia prompted detachment of anti-cancer drug, Methotrexate (MTX), from Co@Au NEs-MTX complex and which triggered 90% decrease in SW620 colon carcinoma cell viability, confirming their application in cancer theranostics. The geometry-based perturbation of cell fate can have a profound impact on our understanding of interactions at nano-bio interface which can be exploited for engineering materials with optimized geometries for superior theranostic applications.
Polyelectrolyte multilayer assembly is one of the most widely applied biomaterial coatings for applications from surface modification, drug delivery, tissue engineering to biomimetic extracellular environment. In this research, we propose a simple layer-wise spin coating technique to prepare chitosan/poly-γ-glutamic acid (C/PGA) polyelectrolyte multilayers (PEMs) on two different biomedical metals, 316L stainless steel (316LSS) and titanium alloy (Ti6Al4V). The multilayer coating was fabricated using oppositely charged chitosan and poly--glutamic acid to deposit a total of 10, 20, or 30 multilayered films. Afterward, tetracycline was loaded by soaking the coated metals for 12 hours. The microstructure, mechanical properties, biocompatibility and drug release rate were investigated by scanning electron microscopy, contact angle measurement, MG63 cell viability and inhibition of Escherichia coli (E. coli) growth. Lastly, MG63 cell attachment was detected by fluorescence microscopy after staining with Hoechst 33258. This coating technique can prepare a layer of 2.2–6.9 m C/PGA PEMs favoring cell attachment and growth. Moreover, tetracycline was released from C/PGA PEMs and inhibited the growth of E. coli. The results suggest that C/PGA PEMs provide a useful platform for modulating the micro-environment for better cell adhesion and antibiotic delivery, which hold great potential for surface modification and drug loading for biomimetic materials.