Direct Reprogramming of Human Suspension Cells into Mesodermal Cell Lineages via Combined Magnetic Targeting and Photothermal Stimulation by Magnetic Graphene Oxide Complexes

Abstract

Suspension cells can provide a source of cells for cellular reprogramming, but they are difficult to transfect by nonviral vectors. An efficient and safe nonviral vector (GO-Fe O -PEI complexes) based on iron oxide nanoparticle (Fe O )-decorated graphene oxide (GO) complexed with polyethylenimine (PEI) for the first time is developed for delivering three individual episomal plasmids (pCXLE-hOCT3/4-shp53, pCXLE-hSK, and pCXLE-hUL) encoding pluripotent-related factors of Oct3/4, shRNA against p53, Sox2, Klf4, L-Myc, and Lin28 into human peripheral blood mononuclear cells (PBMCs) simultaneously. The combined treatment of magnetic stirring and near-infrared (NIR)-laser irradiation, which can promote contact between the complexes and floating cells and increase the cell membrane permeability, respectively, is used to conduct multiple physical stimulations for suspension PBMCs transfection. The PCR analysis shows that the combinatorial effect of magnetic targeting and photothermal stimulation obviously promoted the transfection efficiency of suspension cells. The transfected cells show positive expression of the pluripotency markers, including Nanog, Oct4, and Sox2, and have potential to differentiate into mesoderm and ectoderm cells. The results demonstrate that the GO-Fe O -PEI complex provides a safe, convenient, and efficient tool for reprogramming PBMCs into partially induced pluripotent stem cells, which are able to rapidly transdifferentiate into mesodermal lineages without full reprogramming.

Enhanced Internalization of Nanoparticles Following Ionizing Radiation Leads to Mitotic Catastrophe in MG-63 Human Osteosarcoma Cells

“…In this context, nanoparticle-based drug delivery systems can be designed to pass biological barriers and to target cancerous cells, where they enter and accumulate to reach the drug therapeutic target, while, in the meantime, reducing its systemic toxicity [5,6]. Iron oxide nanoparticles proved to be suitable for such applications due to their biocompatibility for healthy tissues [7] and magnetic targeting ability [8,9]. Moreover, there are several FDA (Food and Drug Administration)-approved systems based on iron oxide nanoparticles for clinical use in cancer treatment through magnetic hyperthermia [10].…”

Graphene Oxide (GO)-based Nanosheets With Combined Chemo/photothermal/Photodynamic Therapy to Overcome Gastric Cancer (GC) Paclitaxel Resistance by Reducing Mitochondria-Derived Adenosine-Triphosphate (ATP)

“…As-prepared GO-PEG-OSA and PTX@GO-PEG-OSA NSs performed remarkable stability compared to the naked GO nanosheets in both water and FBS (Figure 1D; Supplementary les, Figure S1), which was attributed to the higher zeta potentials in contrast to GO and GO-PEG NSs (Figure 1B&C; Supplementary les, Figure S1). Furthermore, as GO-based nano-DDSs represent one of the promising nanomedicines to accomplish the photo-therapy, the photothermal conversion ability was tested by exposure of GO-PEG-OSA NSs and PTX@GO-PEG-OSA NSs (GO-PEG-OSA concentration ~0.1mg/mL) under 808 nm NIR laser irradiation [34]. Signi cant temperature increase (∼8°C and ∼13°C) was observed in GO-PEG-OSA group under NIR irradiation (1 W/cm 2 and 1.5 W/cm 2 ) and PTX@GO-PEG-OSA group showed similar photothermal conversion ability, while free PBS caused only a slight temperature increase (Figure 1G&H).…”

Engineering Biomaterials with Micro/Nanotechnologies for Cell Reprogramming

“…Notably, the cell transfection and reprogramming efficiency were significantly improved by the combined treatment of magnetic stirring and near-infrared photothermal stimulation. 189 Despite the fact that inorganic or hybrid nanoparticles are promising as reprogramming delivery carriers, there are still some critical issues that need to be addressed. First, the loading capability and stability of genes or drugs are limited to a certain extent by surface adsorption.…”