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Abstract
N,N’-Bis(salicylidene)ethylenediamine iron (Fe(Salen)) is an anti-cancer agent with intrinsic magnetic property. Here, we covalently linked Fe(Salen) to paclitaxel (PTX), a widely used anti-cancer drug, to obtain a magnetized paclitaxel conjugate (M-PTX), which exhibited magnetic characteristics for magnet-guided drug delivery and MRI visualization. M-PTX increased apoptosis and G2/M arrest of cultured human oral cancer cell lines in the same manner as PTX. Furthermore, marked contrast intensity was obtained in magnetic resonance imaging (MRI) of M-PTX. In a mouse oral cancer model, a permanent magnet placed on the body surface adjacent to the tumor resulted in distinct accumulation of M-PTX, and the anti-cancer effect was greater than that of M-PTX without the magnet. We believe that this strategy may improve future cancer chemotherapy by providing conventional anti-cancer drugs with novel functionalities such as magnet-guided drug delivery or MRI-based visualization/quantitation of drug distribution.
Highlights
Despite advances in multimodality treatment, e.g. surgery, chemotherapy, and radiation, the prognosis for patients with oral squamous cell carcinoma (SCC) has remained poor, with the overall 5-year relative survival rate of about 50% [1]
In a mouse oral cancer model, a permanent magnet placed on the body surface adjacent to the tumor resulted in distinct accumulation of magnetized paclitaxel conjugate (M-PTX), and the anti-cancer effect was greater than that of M-PTX without the magnet
M-PTX was readily accumulated by a magnet in static and flowing water (Figure 1B and Supplementary Movie 1), as could be seen from the brown color derived from the Fe(Salen) residue
Summary
Despite advances in multimodality treatment, e.g. surgery, chemotherapy, and radiation, the prognosis for patients with oral squamous cell carcinoma (SCC) has remained poor, with the overall 5-year relative survival rate of about 50% [1]. Surgical removal of the cancer is currently the gold standard treatment, but is associated with various complications, such as dysphagia or dysarthria. To preserve organ and function, platinum-based concurrent chemoradiotherapy or bioradiotherapy using cetuximab represents a definitive treatment modality for locally advanced SCC of the head and neck [2, 3]. Acute adverse effects, including hematotoxicities, renal failure, mucositis, dysphagia, or nausea/vomiting, www.oncotarget.com often occur in those patients, who received concurrent high dose cisplatin and radiotherapy. We need to improve the efficacy of such treatments and to decrease these adverse effects
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