While there are a number of available reference and testing materials for micro- and nanoplastic (MNP) studies in toxicology, they are not well-characterized and do not cover all major polymer types that may potentially pollute the environment. This review article will address the question of why we need properly designed synthesized micro- and nanoplastics with a core–shell structure (with organic–inorganic units) and provide researchers with a scientific basis for the design of synthesized MNP particles. It will include a list of commercially available MNPs, an overview of the theoretical background to polymer particle synthesis, and an analysis of the advantages and disadvantages of MNP preparation methods, namely, fragmentation and synthesis, along with examples of synthesized MNP particles. The current study will demonstrate that polystyrene is one of the most prevalent MNP particle types among reference materials from certification bodies and among testing particles synthesized by chemical scientists. Nevertheless, the global industrial production of polystyrene represents approximately 5% of the total, and it is not a dominant plastic type in the textile or packaging industries. In contrast to mechanically fragmented MNP particles, the synthesis approach offers the potential to control the physico-chemical properties, enabling the more selective detection and quantification, as well as a greater comparability of the results amongst toxicological studies.