This article reviews the endocytosis and exocytosis mechanisms of nanoparticles in mammalian cells, emphasizing their importance for the safe and efficient application of engineered nanoparticles in drug delivery and disease treatment. The review covers various sizes, shapes, and surface chemistries of nanoparticles and discusses how these factors influence their cellular uptake and clearance. Key points include: 1. **Nanoparticle Stability**: The surface chemistry of nanoparticles is crucial for their behavior in biological solutions, as it affects their interaction with biomolecules and stability. 2. **Endocytosis Mechanisms**: Nanoparticles can enter cells through clathrin/caveolar-mediated endocytosis, phagocytosis, macropinocytosis, and pinocytosis. The efficiency of endocytosis depends on the nanoparticle's size, shape, and surface chemistry. 3. **Size Effects**: Smaller nanoparticles tend to be more efficiently internalized, and their uptake patterns can vary based on material type and stiffness. 4. **Surface Chemistry**: The surface charge and functionalization of nanoparticles significantly affect their cellular uptake and clearance. Positively charged nanoparticles are more efficiently taken up by macrophages. 5. **Shape Effects**: Spherical nanoparticles are generally more favorable for internalization, while rod-shaped nanoparticles exhibit higher uptake in some cell types. 6. **Exocytosis**: The exocytosis of internalized nanoparticles is influenced by factors such as nanoparticle size, surface chemistry, and the presence of proteins in the medium. 7. **Future Prospects**: Understanding endocytosis and exocytosis mechanisms is essential for developing safer and more effective nanoparticle-based drug delivery systems. The review highlights the need for further research to optimize the design of nanoparticles for clinical applications, particularly in addressing toxicity and improving targeting efficiency.This article reviews the endocytosis and exocytosis mechanisms of nanoparticles in mammalian cells, emphasizing their importance for the safe and efficient application of engineered nanoparticles in drug delivery and disease treatment. The review covers various sizes, shapes, and surface chemistries of nanoparticles and discusses how these factors influence their cellular uptake and clearance. Key points include: 1. **Nanoparticle Stability**: The surface chemistry of nanoparticles is crucial for their behavior in biological solutions, as it affects their interaction with biomolecules and stability. 2. **Endocytosis Mechanisms**: Nanoparticles can enter cells through clathrin/caveolar-mediated endocytosis, phagocytosis, macropinocytosis, and pinocytosis. The efficiency of endocytosis depends on the nanoparticle's size, shape, and surface chemistry. 3. **Size Effects**: Smaller nanoparticles tend to be more efficiently internalized, and their uptake patterns can vary based on material type and stiffness. 4. **Surface Chemistry**: The surface charge and functionalization of nanoparticles significantly affect their cellular uptake and clearance. Positively charged nanoparticles are more efficiently taken up by macrophages. 5. **Shape Effects**: Spherical nanoparticles are generally more favorable for internalization, while rod-shaped nanoparticles exhibit higher uptake in some cell types. 6. **Exocytosis**: The exocytosis of internalized nanoparticles is influenced by factors such as nanoparticle size, surface chemistry, and the presence of proteins in the medium. 7. **Future Prospects**: Understanding endocytosis and exocytosis mechanisms is essential for developing safer and more effective nanoparticle-based drug delivery systems. The review highlights the need for further research to optimize the design of nanoparticles for clinical applications, particularly in addressing toxicity and improving targeting efficiency.