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With superior biocompatibility and unique magnetic properties, iron-based nanoparticles (IBNP) are commonly encapsulated in cells and extracellular vesicles (EV) to allow for magnetic force controlled drug delivery and non-invasive tracking. Based on their natural source and similar morphology, we classify both cells and EVs as being natural lipid encapsulations (NLEs), distinguishing them from synthetic liposomes. Both their imaging contrast and drug effects are dominated by the amount of iron encapsulated in each NLE, demonstrating the importance of magnetic labeling efficiency. It is known that the membranes function as barriers to ensure that substances pass in and out in an orderly manner. The most important issue in increasing the cellular uptake of IBNPs is the interaction between the NLE membrane and IBNPs, which has been found to be affected by properties of the IBNPs as well as NLE heterogeneity. Two aspects are important for effective magnetic labelling: First, how to effectively drive membrane wrapping of the nanoparticles into the NLEs, and second, how to balance biosafety and nanoparticle uptake. In this review, we will provide a systematic overview of the magnetic labeling of NLEs with IBNPs. This article provides a summary of the applications of magnetically labeled NLEs and the labeling methods used for IBNPs. The review also analyzes the role of IBNPs physicochemical properties, especially their magnetic properties, and the heterogeneity of NLEs in the internalization pathway. At the same time, the future development of magnetically labeled NLEs is also discussed.
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