AMF-responsive doxorubicin loaded β-cyclodextrin-decorated superparamagnetic nanoparticles

An alternating magnetic field (AMF)-responsive controlled release system has been developed by the binding of mono-6-deoxy-6-(p-tolylsulfonyl)-beta-cyclodextrin (beta CD-Ts) onto amine-modified superparamagnetic iron oxide nanoparticles (MNP-NH2), resulting in a MNP-beta CD nanocarrier. The structural, chemical and colloidal properties of the nanocarrier MNP-beta CD were fully evaluated by several techniques. Doxorubicin hydrochloride (DOX), as a model anticancer drug, was loaded onto MNP-beta CD resulting in MNP-beta CD-DOX and the release process was investigated by varying the temperature (37 and 45 degrees C), pH (7.4 and 5.0) and presence of an AMF (with and without). DOX can interact with the negatively charged surface of MNP-beta CD and also with the cavity of beta CD forming inclusion complexes. Under acidic conditions, both the negatively charged surface of MNP-beta CD and the ionizable groups of DOX are protonated and the interactions between DOX and the nanocarrier MNP-beta CD are weakened, thus, accelerating drug release. Temperature increase can reduce the supramolecular interactions between DOX and the nanocarrier MNP-beta CD, favoring DOX release. Thermo-induced burst release at 45 degrees C has been investigated either by applying an alternating magnetic field (AMF, f = 307 kHz) or heating the solution in a thermostatic cuvette holder. In the absence of an AMF at 45 degrees C and at the pH value of the lysosome (5.0), 92% of DOX was released into the solution within 6 h. Importantly, in an AMF, at 45 (+/- 1)degrees C and pH = 5.0, the same percentage of DOX release was observed after 50 min. Furthermore, in vitro assays revealed that the unloaded MNP-bCD nanoparticles (100 mu g mL(-1)) displayed negligible cytotoxicity against A549 human lung adenocarcinoma cells either in the absence or presence of an AMF (H x f = 4.9 x 10(9) A m(-1) s(-1)) applied for 30 min on the cells. In the presence of an AMF no macroscopic temperature variation was detected in the wells containing the cells incubated with DOX unloaded MNP-beta CD nanoparticles. The same amount of DOX loaded nanoparticles (MNP-beta CD-DOX) showed cytotoxicity only in the presence of an AMF (H x f = 4.9 x 10(9) A m(-1) s(-1) applied for 30 min), inducing cell death. Also, no macroscopic temperature variation was detected; therefore, DOX release might be associated with local heating generated from the rotation movements of the nanoparticles (Brown relaxation) upon AMF application. Thus, the DOX loaded beta-cyclodextrin-decorated superparamagnetic nanoparticles (MNP-bCD-DOX) are a potential controlled drug release agent with cancer-killing properties under an AMF.