Macrophages co-loaded with drug-associated and superparamagnetic nanoparticles for triggered drug release by alternating magnetic fields

Two features of macrophages make them attractive for targeted transport of drugs: they efficiently take up a broad spectrum of nanoparticles (NPs) and, by sensing cytokine gradients, they are attracted to the sites of infection and inflammation. To expand the potential of macrophages as drug carriers, we investigated whether macrophages could be simultaneously coloaded with different types of nanoparticles, thus equipping individual cells with different functionalities. We used superparamagnetic iron oxide NPs (SPIONs), which produce apoptosis-inducing hyperthermia when exposed to an alternating magnetic field (AMF), and co-loaded them on macrophages together with drug-containing NPs (inorganic-organic nanoparticles (IOH-NPs) or mesoporous silica NPs (MSNs)). We show that individual macrophages can take up both SPIONs and drug-loaded NPs efficiently, thereby generating drug-loaded cells susceptible to AMF-induced cell death. Macrophages co-loaded with SPIONs and drug-containing IOH-NPs spontaneously released the drugs at similar rates irrespective of the application of an AMF. Notably, while the spontaneous drug release from macrophages co-loaded with SPIONs and drug-associated MSNs was low, AMF exposure accelerated the drug release. Thus, AMF exposure of SPION/drug-MSN coloaded macrophages provides a simple strategy for trigger-controlled drug release since it does not require any chemical modification of NPs or drugs. Thus, we assume that the coloading of different types of NPs will expand the potential of macrophages for drug delivery.