Desai Omkar, Kumar Sandhya, Köster Mario, Ullah Sami, Sarker Sushobhan, Hagemann Valentin, Habib Mosaieb, Klaassen Nicole, Notter Silke, Feldmann Claus, Ehlert Nina, Hauser Hansjörg, Wirth Dagmar
Model System for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124, Braunschweig, Germany.
Institute of Inorganic Chemistry, Leibniz University Hannover, Callinstraße 9, 30167, Hannover, Germany.
Drug Deliv Transl Res. 2025 Jan 13. doi: 10.1007/s13346-024-01774-9.
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.
它们能高效摄取多种纳米颗粒（NPs），并且通过感知细胞因子梯度，被吸引至感染和炎症部位。为了拓展巨噬细胞作为药物载体的潜力，我们研究了巨噬细胞是否能够同时负载不同类型的纳米颗粒，从而使单个细胞具备不同的功能。我们使用了超顺磁性氧化铁纳米颗粒（SPIONs），其在交变磁场（AMF）作用下会产生诱导细胞凋亡的热疗效果，并将其与载药纳米颗粒（无机 - 有机纳米颗粒（IOH - NPs）或介孔二氧化硅纳米颗粒（MSNs））共同负载于巨噬细胞上。我们发现单个巨噬细胞能够高效摄取SPIONs和载药纳米颗粒，从而产生对AMF诱导的细胞死亡敏感的载药细胞。负载有SPIONs和含药IOH - NPs的巨噬细胞会以相似的速率自发释放药物，而与是否施加AMF无关。值得注意的是，虽然负载有SPIONs和药物相关MSNs的巨噬细胞的自发药物释放量较低，但AMF暴露会加速药物释放。因此，对负载有SPION/药物 - MSN的巨噬细胞进行AMF暴露提供了一种触发控制药物释放的简单策略，因为它不需要对纳米颗粒或药物进行任何化学修饰。因此，我们认为负载不同类型的纳米颗粒将拓展巨噬细胞在药物递送方面的潜力。
