The potential of atomic force microscopy: from nanoparticle characterization to drug delivery implications

Comprehensive nanoparticle (NP) characterization and its interactions with cells are critical for the successful development of effective drug delivery systems (DDS). In this context, atomic force microscopy (AFM), a high-resolution technique, provides relevant information about NP properties, such as topography, size, stiffness, and viscoelasticity at the nanoscale level. The knowledge and correlation of these parameters enable rational design of NPs with tailored and controlled properties to target specific cells and/or tissues, making AFM a powerful tool for nanotechnology research. This review explores and discusses the features of AFM in providing high-resolution images of NP surfaces, as well as size and mechanical properties measurements. Through critical analysis, the challenges and limitations inherent in AFM-based NP characterization (e.g. tip convolution, slow acquisition speed, and sample preparation artifacts) are addressed, and the correlation between mechanical properties of NPs with their interactions in biological systems is discussed. This review adopts a broad approach, aiming to guide researchers in experimental design and to provide an updated perspective on the applicability and advancements of AFM in the drug delivery field.