Advancing Nanomedicine Through Electron Microscopy: Insights Into Nanoparticle Cellular Interactions and Biomedical Applications

Nanomedicine has revolutionized cancer treatment by the development of nanoparticles (NPs) that offer targeted therapeutic delivery and reduced side effects. NPs research in nanomedicine significantly focuses on understanding their cellular interactions and intracellular mechanisms. A precise understanding of nanoparticle interactions at the subcellular level is crucial for their effective application in cancer therapy. Electron microscopy has proven essential, offering high-resolution insights into nanoparticle behavior within biological systems. This article reviews the role of electron microscopy in elucidating the cellular uptake and intracellular interactions of NPs. Transmission electron microscopy (TEM) provides imaging capabilities, such as cryo three-dimensional tomography, which offer in-depth insights into nanoparticle localization, endocytosis pathways, and subcellular interactions, while high resolution-TEM is primarily used for studying the atomic structure of isolated NPs rather than nanoparticles within cells or tissues. On the other hand, scanning electron microscopy (SEM) is ideal for examining larger surface areas and provides a broader perspective on the morphology and topography of the samples. The review highlights the advantages of electron microscopy in visualizing nanoparticle interactions with cellular structures and tracking their mechanisms of action. It also addresses the challenges associated with electron microscopy characterization, such as tedious sample preparation, static imaging limitations, and a restricted field of view. By examining various nanoparticle uptake pathways, and cellular destination of NPs with examples, the article emphasizes the importance of these pathways to optimize nanoparticle design and enhance therapeutic efficacy. This review underscores the need for continued advancement in electron microscopy techniques to improve the effectiveness of nanomedicine and address existing challenges. In summary, electron microscopy is a key tool for advancing our understanding of nanoparticle behavior in biological contexts, aiding in the design and optimization of nanomedicines by providing insights into nanoparticle cellular dynamics, uptake mechanisms, and therapeutic applications.