Abstract
In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)–photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF–NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH–PT dual magneto-photothermal cancer therapy.
Highlights
Various treatment modalities are available for cancers, each method has certain limitations
We further evaluated the cytotoxicity of magnetic liposomes (MLs) after alternating magnetic field (AMF) and NIR laser treatments using flow cytomWeteryfuanrtahleyrsiesv. aTlhueatceedllsthweecryetsottaoixniecditywoitfhMALnsneaxftienrVA/PMI FtoaenxdamNiInRe ltahseerpetrrecaetnmtaegnetsofulsiivneg(Qflo3w), ecayrtlyomapetorpytaontiacly(Qsi4s.),Tlhaetecaepllos pwtoerteics(tQai2n)e,danwditnheAcrnontiecxicnelVls/P(QI t1o) eaxcacomridniengthteopdeirffceernetnagceesoifnlipvleas(Qm3a), membrane permeability and integrity (Figure 10)
Using the thin-film hydration method, we successfully optimized the preparation of cationic MLs, using the EE of coated iron oxide magnetic nanoparticles (CMNPs) and size of MLs as the responses
Summary
Various treatment modalities are available for cancers, each method has certain limitations. The unique multifunctional features provided by nanoparticles may overcome the efficacy limitations from current cancer therapies and open up new avenues of treatment, as has been shown recently with the rising field of nanomedicine in cancer therapy [1]. One of the examples of nanomedicines for the therapeutic treatment of cancer is to employ energy-absorbing nanoparticles for hyperthermia- or heat-mediated therapy [2]. By focusing energy from an external source, nanoparticles can act as a heat source intratumorally and lead to the death of cancer cells [3,4]. By acting as a remotely controllable local heat mediator without profoundly affecting the physiological temperature of surrounding healthy tissues, hyperthermia provided by nanoparticles could lead to tumor ablation by shrinking tumors through destroying tumor cells or damaging proteins and structures within cancer cells [7]
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